The mental health challenges associated with HIV/AIDS have evolved and changed as the dynamics of the epidemic have developed. This chapter emphasizes how the mental health issues associated with the epidemic have been significantly affected by changes in disease context. After HIV was identified as the cause of AIDS and reliable serological tests were developed, there followed a period when only prophylaxis for opportunistic infections was available. Psychological aspects of HIV testing illustrate how important it is to consider changing contexts in the discussion of mental health and HIV. Disclosure of HIV-positive status can be a psychologically consequential decision. A large literature now exists regarding the impact of HIV/AIDS-related stresses on various psychological and biological outcomes. The high levels of need found in many populations with HIV have meant that efforts to develop comprehensive care systems have sometimes produced ironic results.