The Amazon region is known for its vastness and complex ecosystem. Nevertheless, this area is also the habitat of a considerable human contingent. Even though a large part of this population is concentrated in the urban areas, millions of people also live in the rural areas. These populations include several indigenous groups, traditional populations such as the caboclos and the quilombolas, and recent immigrants from several parts of Brazil. However, little is still known about these groups and even less about their health and environmental sanitation situation. This article provides an overview of some of the major challenges to the health of the Amazon populations and presents examples of the precarious situation of some rural groups. It is shown that in this region it will not be possible to reach the Millenium Objectives in the currently proposed timeframe, and some proposals for public policies in the areas of health and the environment are presented which, if implemented, will improve the health of the Amazonian populations and help to simultaneously promote environmental protection.