A cross-sectional study of knowledge, attitudes, beliefs, and practices (KABPs) toward HIV and antiretroviral therapy (ART) was conducted in Soweto, South Africa, using a standardized validated questionnaire. Of 105 HIV clinic patients evaluated, 70% of whom were not on ART, 89% had good knowledge about the cause of HIV infection and 83% knew about modes of transmission. Fifty-nine percent reported they were not worried about ART side effects. Sixty-five percent agreed that missing ART doses can lead to disease progression. Ninety percent had disclosed their HIV serostatus to 1 or more persons, but only 62% of those with a current sexual partner reported having told that partner. Approximately 80% reported that if they were taking ART, they would not be worried about family or friends finding out. Forty-nine percent believed that ART can cure HIV, a belief that was associated with a low level of education (P < 0.001). Overall, knowledge of the cause of HIV/AIDS, modes of transmission, and importance of ART adherence was good in our study population. Further research is warranted to assess the extent to which this knowledge and attendant attitudes predict ART adherence levels. The low rate of HIV serostatus disclosure to sexual partners calls for multidimensional interventions to reduce HIV-related stigma.