Africa bears a disproportionate burden of NCDs, including CVDs, having one of the highest morbidity and mortality rates globally. As the burden of CVDs such as stroke, heart failure, and coronary artery disease increase, endemic conditions, for example, rheumatic heart disease and endomyocardial fibrosis persist. NCD mortality is projected to surpass communicable disease mortality. This increase is driven by a rise in risk factors attributable to the epidemiological transition. Control of communicable diseases has been prioritized leading to remarkable declines in communicable, maternal, neonatal and nutritional (CMNN) diseases. There hasn’t been commensurate attention to control of CVDs. In the context of poor, under resourced health care systems, geared towards communicable diseases, control of CVDs poses unique challenges. A multipronged strategy is needed to tackle the challenges. These include a skilled workforce across all cadres; team-based care with appropriate task shifting, relevant practice guidelines with clear referral pathways; strengthening of primary health care; evidence-based prevention strategies and contextually relevant research. Specific attention is needed for sex- and gender-specific challenges. This requires the collaborative effort of all stakeholders, including governments, professional organizations, academia, civil societies, international organizations, and most importantly the community.