The theory of syndemics has been widely applied in HIV-prevention studies of gay, bisexual, and other MSM (men who have sex with men) over the last decade. Our investigation is the first to consider the applicability of the theory in a sample of aging (ages 50 and over) HIV-positive MSM, which is a growing population in the United States. A sample of 199 men were actively recruited and assessed in terms of mental health and drug-use burden, as well as sexual risk behaviors. Bivariate and multivariable analyses indicate a high level of association between psychosocial burdens (i.e., drug use and mental health) and same-sex unprotected sexual behaviors, providing initial support for the applicability of the theory of syndemics to this population. Further support can be seen in participants’ narratives. Findings suggest the mutually reinforcing nature of drug use, psychiatric disorders, and unprotected sexual behavior in older, HIV-positive, gay, bisexual, and other MSM, highlighting the need for holistic strategies to prevention and care among this population of older and sexually active individuals. In short, the generation of gay men who came of age in the late 1970s and 1980s, “the AIDS Generation,” are continuing to mature such that further efforts must be enacted to meet the multidimensional nature of these men's physical, mental, and sexual health needs.