Helminth infections affect over a quarter of the world's population, especially in the developing countries. These long-lasting parasitic infections cause widespread immune activation and dysregulation, a dominant Th2 cytokine immune profile and an immune hyporesponsiveness state. Considering these profound immune changes and the similar geographic distributions of helminthic infections, HIV and tuberculosis (TB), we suggest that helminthic infections play a major role in the pathogenesis of AIDS and TB. They apparently make the host more susceptible to infection by HIV and Mycobacterium tuberculosis, and impair his/her ability to generate protective immunity against both infections. The implication of these ideas is that without eradication of helminth infections and/or modulation of the immune changes that they cause, HIV and TB vaccines may fail to confer protection against their respective infections in helminth-endemic areas.