Men who have sex with men experience high rates of psychosocial health problems such as depression, substance use, and victimization that may be in part the result of adverse life experiences related to cultural marginalization and homophobia. These psychosocial health conditions interact to form a syndemic which may be driving HIV risk within this population. However, MSM also evidence great resilience to both the effects of adversity and the effects of syndemics. Investigating and harnessing these natural strengths and resiliencies may enhance HIV prevention and intervention programs thereby providing the additional effectiveness needed to reverse the trends in HIV infection among MSM.