High rates of depression have been observed among men who have sex with men (MSM) relative to the general adult male population; however, a dearth of research has explored depression among Black MSM. Black MSM (n = 197) recruited via modified respondent-driven sampling between January and July 2008 completed an interviewer-administered quantitative assessment and voluntary HIV counseling and testing. Bivariate and multivariable logistic regression procedures examined the associations of demographics, behavioral HIV risk factors, and psychosocial variables with depressive symptoms by severity, using the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). Adjusting for demographic and behavioral variables, significant factors associated with (1) clinically significant depressive symptoms (33%; CES-D score > or = 16): being publicly insured by Medicaid, having serodiscordant anal sex with a casual male partner, and being diagnosed with an STD in the prior 12 months; (2) moderate depressive symptoms (19%; CES-D score 16-26): having serodiscordant unprotected anal sex with a casual male partner and being diagnosed with an STD in the prior 12 months; (3) severe depressive symptoms (14%; CES-D score 27+): being publicly insured by Medicaid and reporting difficulty accessing healthcare in the past 12 months. Moderately depressed Black MSM may be more likely to engage in behaviors that place them at increased risk for HIV and other STDs. HIV prevention interventions for Black MSM may benefit from incorporating screening and/or treatment for depression, allowing MSM who are depressed to respond more effectively to behavioral change approaches.