One of the coolest and still off the beaten path adventures you can do on Amazon river is to travel from town to town on cargo boats. River commerce/delivery of goods is quite active, and for some Amazon river communities getting supplies by boat is the only way due to the fact that they are too remote and too disconnected from the more advanced road infrastructures. In fact, if you want to get by land from Colombian side of Amazon to the Peruvian mountains that border Amazon jungle - river is the only way, there are no roads.
To start our Amazon adventures we flew from Bogota into Leticia, Colombia - a tiny town in the middle of dense jungle, cut off from the rest of the country by guerrilla forces predominant in the jungle. Leticia is a funny town - it's in Colombia, but from Leticia you can walk into Brazil (3 blocks from the town center) and you can hang out in Peru (5 minutes boat ride). There are only few cars in town as there are no roads connecting Leticia to anything else, it's mostly motorbikes. There's not much around, but you can explore the local villages, communities and jungle conservation projects by renting motorbikes ($12 a day) - everything feels like in the middle of nowhere though.
We stayed at Mahatu hostel - it's really nice, affordable, has a lot of green, and the owner is a great guy who knows the jungle and surroundings inside out (he'll also recommend where to get the best set menus in town)
There are several agencies that organize trips into the jungle, watching wildlife and staying in indigenous communities, but many travelers come here for the sole purpose of boarding a cargo boat to cross into Peru. There is a faster and more "upscale" boat that can take you to Iquitos in Peru (within 24 hrs) even though "upscale" is hard to apply to anything in the jungle. And there are local cargo boats that go to Iquitos about 4 times a week and take 4 days/3 nights(ask around to know the precise days or visit the port to confirm the schedule)
For the true spirit of adventure we chose the cargo boat. The trip from Leticia to Iquitos is less tried by foreigners, so the prices are lower - the 3 nights trip + food + sharing a cabin costs about $45, but you can bargain with the captain. The trip from Iquitos to Yurimaguas where the overland road starts - was about $70 per person, but it also depends on how many foreigners you find who wants to share a cabin.
A cargo boat is a barge with an engine - base floor is for cargo, there's really nothing you can't encounter being transported - bananas, soda bottles, tractors, pigs, furniture, rice, motorbikes, other boats, plastic, etc. Second and third floor is for passengers - the space is just a deck with metal bars on the ceiling for tying up hammocks. Everyone hangs their own hammock - sometimes it's reasonable distance from each other and sometimes when the boat is crowded it's more like shoulder to shoulder - and everyone lives in their hammock for 4 days. You can buy a decent hammock and ropes at Leticia market for $8-12. Before boarding the boat - you need to get an exit stamp from Colombian Immigration (you'll need to go for it to the airport border control) and an entry stamp from Peruvian Immigration (you'll need to take a boat to a small Peruvian island next to Leticia called Santa Rosa and go to Immigration office/shack on the main street, any boat from the port will take you there for about $2-3, from that island you can take another boat to the neighboring island where you can get onboard of your boat)
There are mosquitos in all villages along the Amazon, but when you're on the boat and moving no need to worry about them/no need for mosquito net - the breeze and distance from the shore keeps them away.
There is a kitchen onboard and they serve breakfast, lunch and dinner (for breakfast usually just bread, for lunch and dinner - rice, fried banana and some undistinguishable meat) Some gringos (white people) who traveled on cargo boats will advise not to eat the food onboard as you can get upset stomach or even parasites because of the quality of the water they use and seasoned sailor style hygiene standards, but we and the other couple of travelers took the chance and ate some of the food they serve (not meat though) It's very basic and the portions are quite small - so take canned tuna, bread, snacks, vegetables and water with you. At many stops there will be vendors sweeping through the deck selling food while the boat is ashore, so you can get fruit and snacks from them too (you never know though when they'll come) You can use plates and utensils from the kitchen or you can get your own plate and fork at the market (it's still a mystery whether they use filtered or unfiltered/water from the river for washing dishes)
There are stories of bags being stolen from gringos while they were sleeping. On one of the boats we were also warned by some good locals on board that there is a guy onboard who is famous for stealing and had already problems with police. So if you have nothing to steal keeping a bag next to your hammock or inside your hammock will be fine, but if you have your DSLR, tablet, kindle, expensive gear in your bag - the advice is to share a cabin with other travelers. The cabin is an absolute no-no for sleeping (there is a bunk bed in each of 8-10 cabins onboard), but you can sleep on the deck in your hammock and just use the cabin to keep your bags locked there. On the day of departure the boat will be offloading and loading at least 4 hours before departure (usually 6:30-8pm) so you can come 3 hours before in order to find a good spot for the hammock (upper deck is the best as toilets and kitchen is on lower deck) and to find a captain to bargain for a cabin. When you get a cabin and keys from the captain you can stay and watch for other foreigners to arrive and offer them to share the cabin/costs for the bags. From Leticia we were 3 gringos onboard, from Iquitos - there were about 10 foreigners in total so we ended up with a pretty good deal of sharing the cabin between 3 the first trip and between 5 the next trip.
People traveling on cargo boats are mostly villagers from remote places and traveling as far as from the East of Brazil to the West of Peru on cargo boats (2-3 weeks just to visit a family in another country) Most of them are very simple people and a lot of them have never seen a white person before - so be sure, you'll be quite an attraction on the boat. If you speak at least basic Spanish - you can get to know some people onboard, especially your neighbors in the closest hammocks (even though your neighbors might change every day as they come and go)
The boat experience is really unique. You get to see places and communities which you'd never see otherwise as there are no roads. You get to experience the magnitude and majesty of the Amazon river itself - it's length that goes beyond the horizon, its width and fullness that impresses you every morning when you open your eyes, its abundant green color on both banks. With every kind of weather the Amazon changes - from gloomy and mysterious to incredibly bright colors and lively atmosphere. The time on the boat passes very slowly, most of the time you're going to be walking around, sleeping or reading in your hammock or talking to others. There's nowhere to go, there's nothing to do and there's nothing you can do about anything on the boat - you're stuck there for 4 days and this being stuck is quite liberating.
There are of course other interesting aspects of being on the boat. The hygiene in the toilets and showers may seem close to non existent (take wet wipes instead of using showers), the local kids will immediately take over the boat as their playground, you might get a transvestite cook or a waiter flirt with you occasionally (for some reasons all Amazon river cargo boats employ transvestites and not the elite looking ones), time to time you'll have to defend your hammock spot when someone will attempt to hang theirs right above you, and so on. But it's fun!
The boat never sleeps and that's the life on the boat.