WHO expects the burden of cancer in sub-Saharan Africa to grow rapidly in coming years and for incidence to exceed 1 million per year by 2030. As a result of late presentation to health facilities and little access to diagnostic technology, roughly 80% of cases are in terminal stages at the time of diagnosis, and a large proportion of patients have moderate to severe pain that needs treatment with opioid analgesics. However, consumption of opioid analgesics in the region is low and data suggest that at least 88% of cancer deaths with moderate to severe pain are untreated. Access to essential drugs for pain relief is limited by legal and regulatory restrictions, cultural misperceptions about pain, inadequate training of health-care providers, procurement difficulties, weak health systems, and concerns about diversion, addiction, and misuse. However, recent initiatives characterised by cooperation between national governments and local and international non-governmental organisations are improving access to pain relief. Efforts underway in Uganda, Kenya, and Nigeria provide examples of challenges faced and innovative approaches adopted and form the basis of a proposed framework to improve access to pain relief for patients with cancer across the region.