With non-communicable diseases (NCDs) projected to become leading causes of morbidity and mortality in developing countries, research is needed to improve the primary care response, especially in sub-Saharan Africa. This region has a particularly high double burden of communicable diseases and NCDs and the least resources for an effective response. There is a lack of good quality epidemiological data from diverse settings on chronic NCD burden in sub-Saharan Africa, and the approach to primary care of people with chronic NCDs is currently often unstructured. The main primary care research needs are therefore firstly, epidemiological research to document the burden of chronic NCDs, and secondly, health system research to deliver the structured, programmatic, public health approach that has been proposed for the primary care of people with chronic NCDs. Documentation of the burden and trends of chronic NCDs and associated risk factors in different settings and different population groups is needed to enable health system planning for an improved primary care response. Key research issues in implementing the programmatic framework for an improved primary care response are how to (i) integrate screening and prevention within health delivery; (ii) validate the use of standard diagnostic protocols for NCD case-finding among patients presenting to the local health facilities; (iii) improve the procurement and provision of standardised treatment and (iv) develop and implement a data collection system for standardised monitoring and evaluation of patient outcomes. Important research considerations include the following: selection of research sites and the particular NCDs targeted; research methodology; local research capacity; research collaborations; ethical issues; translating research findings into policy and practice and funding. Meeting the research needs for an improved health system response is crucial to deliver effective, affordable and equitable care for the millions of people with chronic NCDs in developing countries in Africa.