Understanding challenges to virologic suppression is essential to optimizing health outcomes among individuals with HIV. This cross-sectional behavioral assessment was conducted among 514 individuals presenting at an urban U.S. HIV clinic between June and September 2007. The majority of the sample was African American and male, with a mean age of 42 years. Most of the sample was receiving highly active antiretroviral therapy (HAART), and the majority of those had suppressed viral loads (HIV viral loads less than 400 copies per milliliter). By logistic regression analyses, African American/other minorities had 2.9 increased odds, those less than high school degree had 2.3 increased odds, those who were receiving ritonavir-boosted protease inhibitor therapy had 1.4 increased odds, and those who had expressed symptoms indicative of depressive disorders had 2.5 increased odds of having unsuppressed viremia as compared to Caucasians, those with more education, receiving non-nucleoside reverse transcriptase inhibitor-based therapy, and who had minimal depressive symptoms, respectively. These findings signify the importance of individualized interventions to enhance virologic suppression, both based on medication choices and individual characteristics.