Although improvements in human health represent a crucial aspect of development worldwide, many trends associated with development and global change appear to be reducing health security. In this article, we define the human epidemiological environment and describe key biophysical, economic, sociocultural, and political factors that shape it. The potential impact upon the epidemiological environment of aspects of both development and global change are then examined: the influences of human population size, mobility, geographic distribution, and nutritional status; modernization; loss of indigenous medicinal knowledge; microbial evolution of antibiotic resistance; land conversion and biodiversity loss; agricultural intensification; stratospheric ozone depletion; and climate change. Human vulnerability to infectious disease is often strongly and deleteriously influenced by ongoing, intensifying changes in these factors. An unprecedented level of communication and cooperation between experts, institutions, and nations is required to respond to the increasing threat of epidemic disease, which points to a promising area for enhanced interdisciplinary collaboration.