Despite continued advances in HIV prevention and treatment, gay and bisexual men and other men who have sex with men (MSM) remain the population most impacted by HIV/AIDS in the US and many other Western countries. Additionally, MSM are disproportionately affected by various psychological problems, including depression, distress, trauma and substance use. These challenges frequently co-occur, and are associated with higher rates of behaviours related to HIV acquisition and transmission, HIV infection, and, for those living with HIV/AIDS, lower levels of treatment engagement. Moreover, racial disparities exist among MSM in the US; for example, young African American MSM bear a disproportionate burden of the continuing HIV epidemic, likely related to disparate HIV prevalence in partner pools as well as long-standing structural inequities. In this review, the mental health challenges facing MSM primarily in the US, related to HIV and STI prevention and across the HIV care cascade, including HIV diagnosis, engagement and retention in care, and antiretroviral adherence, are illustrated. Disparities among MSM including racial and ethnic, age-related and structural barriers associated with HIV prevention and treatment, as well as current interventions, are also described. Moving forward towards 2020, resources will be needed to assess and implement scalable intervention strategies to address psychological and social barriers to HIV and STI risk reduction and treatment for MSM, with a particular focus on the most vulnerable subpopulations. As access to prevention and treatment strategies expand, and new breakthroughs continue to emerge, behavioural strategies will continue to be needed to reduce risk and increase uptake and engagement among MSM most at risk through 2020 and beyond.