This paper describes findings from a recent study examining how people affected directly and indirectly by the HIV/AIDS epidemic cope with HIV-related illness in Mexico. One-hundred-and-thirteen in-depth interviews were conducted with key informants in two contrasting communities: Ciudad Netzahualcóyotl (an economically marginalized community) and the gay community in Mexico City (a sexually marginalized community). This paper describes the AIDS-related wellness/illness careers or trajectories followed by individuals in both communities, and identifies critical points for material and emotional intervention. This career comprises four stages: (1) life before infection; (2) life surrounding the discovery of seropositivity; (3) living as an HIV-positive person; and (4) facing death. Comparisons are drawn between the processes of adjustment and coping found in both communities. In Ciudad Netzahualcóyotl, wellness/illness careers are closely linked to prevailing poverty and oppression, as well as the sense of urgency in which local people live their lives. In the case of the gay community, wellness/illness careers are associated with the intolerance and social repression faced by homosexual men. The paper concludes by suggesting possible interventions to improve the lives of people with HIV/AIDS in Mexico today.