Adding to a traditional stress perspective, behavioral medicine has been focusing increasingly on investigating the potential impact of positive psychosocial factors on disease course in HIV. Dispositional optimism, active coping, and spirituality show the most evidence for predicting slower disease progression, although the data are not entirely consistent. Findings for the role of social support are mixed, although indications are that it may be particularly helpful at later stages of illness. Many of the other constructs (positive affect, finding meaning, emotional expression/processing, openness, extraversion, conscientiousness, altruism, and self-efficacy) have only been examined in one or two studies; results are preliminary but suggestive of protective effects. Plausible behavioral and biological mechanisms are discussed (including health behaviors, neurohormones, and immune measures) as well as suggestions for clinicians, limitations, future directions, and a discussion of whether these constructs can be changed. In conclusion, investigating the importance and usefulness of positive psychosocial factors in predicting disease progression in HIV is in its beginning scientific stages and shows good initial evidence and future promise.