Africa is confronted by a heavy burden of communicable and non-communicable diseases. Cost-effective interventions that can prevent the disease burden exist but coverage is too low due to health systems weaknesses. This editorial reviews the challenges related to leadership and governance; health workforce; medical products, vaccines and technologies; information; financing; and services delivery. It also provides an overview of the orientations provided by the WHO Regional Committee for Africa for overcoming those challenges. It cautions that it might not be possible to adequately implement those orientations without a concerted fight against corruption, sustained domestic and external investment in social sectors, and enabling macroeconomic and political (i.e. internally secure) environment.