These days, nearly all Amazon river cruises travel upstream from Iquitos to the confluence of the Ucayali and Marañon Rivers, and the Pacaya-Samiria Reserve. However, when I first took one of these cruises, in the year 2002, the Rio Amazonas took me and my group downstream to the tri-border with Colombia and Brazil. It remains a very interesting - albeit busier - river journey, which can be visited using local transport or by chartering your own vessel.
Amazon River on Local Transport
Iquitos is well-known as being the most remote city in the world, only accessible by air or river.
For those wanting to experience the latter, there are several ways of going about it.