Despite advances in HIV treatment, there continues to be great variability in the progression of this disease. This paper reviews the evidence that depression, stressful life events, and trauma account for some of the variation in HIV disease course. Longitudinal studies both before and after the advent of highly active antiretroviral therapies (HAART) are reviewed. To ensure a complete review, PubMed was searched for all English language articles from January 1990 to July 2007. We found substantial and consistent evidence that chronic depression, stressful events, and trauma may negatively affect HIV disease progression in terms of decreases in CD4 T lymphocytes, increases in viral load, and greater risk for clinical decline and mortality. More research is warranted to investigate biological and behavioral mediators of these psychoimmune relationships, and the types of interventions that might mitigate the negative health impact of chronic depression and trauma. Given the high rates of depression and past trauma in persons living with HIV/AIDS, it is important for healthcare providers to address these problems as part of standard HIV care.