Clinical trials in oncology are an emergent field in sub-Saharan Africa. There is a long history of clinical trials in high-income countries (HICs), with increasing attempts to develop patient-centric approaches and to evaluate patient-centered outcomes. The challenge remains as to how these trends could be adopted in low-resource settings and adapted to best fit the different health ecosystems that coexist on the African continent. Models that evaluate patient-related outcomes and measures and that are used in HICs must be modified, adopted, and adapted to suit the diverse populations and the low-resource settings in most of the continent. Patient engagement in clinical trials in Africa must be well nuanced, and it demands innovation and application of models that consider established but tailored notions/principles of patient and community engagement and the unique sociocultural aspects of different populations. It also must be linked to strategies that aim to improve patient education, health literacy, and access to services and to encourage and protect patient autonomy.