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Traditionally, substance use services have not been provided by South African primary health care facilities, limiting access to treatment. A lack of mental health workers has slowed plans to integrate these services into the primary health care system. This has prompted calls for the task-shifting of some treatment responsibilities from mental health specialists to non-specialty health workers. We present findings from three projects that used a task-shifting approach to integrate brief interventions (BIs) for substance use into primary care. The first involved the horizontal integration of nurse-led BI services. In our three-month evaluation, we found significant reductions in substance use (p < 0.001). The second involved the vertical integration of a community health worker-delivered BI within emergency services. In a randomized controlled trial, participants were assigned to a session of motivational interviewing (MI), a five-session blended MI and problem-solving therapy (PST) intervention, or a control group. At three months, ASSIST scores were significantly lower in the MI-PST group than in the other groups (p < 0.001). In the third, we horizontally integrated a nurse-delivered BI intervention into an antenatal clinic. There was low detection of alcohol use; however, tobacco use decreased significantly following the intervention (p < 0.001). Through task-shifting, it is feasible to provide substance use services in primary health care in low- and middle-income countries. It remains unclear whether it is more feasible, acceptable, and effective to integrate these services into primary care using horizontally or vertically integrated approaches. These questions need to be answered in order to guide the implementation of these new health services.