Besides hypoxia, high altitude settings are characterised by other peculiar environmental factors, such as cold and ultraviolet radiation. In addition, there are prevalent environmental changes driven mainly by human activity, including climate change in the highland Andes, and outdoor and indoor pollution. Also, poverty and childhood malnutrition are rampant in high altitude human settlements. The role of these additional environmental factors in the modification of responses to life at high altitudes and the resulting health status of individuals and populations is an area largely neglected in high altitude research. We will review in this paper how high altitude hypoxia and other environmental factors prevailing at high altitude can affect organisms living in highlands, with particular emphasis on human beings. The available evidence on effectiveness of interventions for mitigating or reversing the negative impact of such influences will also be discussed. © 2008, Inderscience Publishers.