The rapid assessment aimed to describe drug use and sexual practices that place injection and noninjection drug users (IDUs/NIDUs) at risk for HIV in South Africa. The sample comprised 85 key-informant (KI) and focus-group (FG) interviewees in or serving locations with high levels of drug use in Cape Town, Durban, and Pretoria. HIV testing of drug-using KIs was conducted using the SmartCheck Rapid HIV-1 Antibody Test. The findings indicated that commonly used drugs had differing effects on sexual and drug-use practices. Risky injecting behaviors among IDUs were common, and most interviewees engaged in sex when on drugs, some without condoms. These behaviors were also influenced by trust in intimate relationships. Injection drug users seemed more knowledgeable about HIV transmission than NIDUs, and 20% of IDUs who agreed to HIV screening tested positive. Views about drug- and HIV-intervention services, accessibility, and their efficacy were mixed. The findings suggest greater synergy is needed between drug- and HIV-intervention sectors and that consideration should be given to making various risk-reduction strategies more accessible. The study's limitations have been noted.