We describe the initiation and establishment of The University of Zambia - University College London Medical School (UNZA-UCLMS) Research and Training Project, an entirely African scientist-led, south-north partnership. In its 16 year existence, the project, by successfully obtaining competitive grant funding, has transformed itself into one of Africa's most productive African-led R&D programmes with training and visible research outputs. The project serves as a role model and now networks R&D and training activities with six southern African (10 institutions) and six European countries. This project case study illustrates that deep commitment is essential for success and that the factors which facilitate success in R&D in Africa need to be evaluated. The long-term prospects for sustaining the UNZA-UCLMS Project appear bright and are dependent on several factors: the ability to retain trained African scientists; obtaining continued competitive or donor grant funding support; and serious investment by the African governments involved. The recent 255 million Euros EDCTP investment in sub-Saharan Africa through south-north partnerships is expected to enhance existing African-led R&D programmes. African governments and scientists must rise to the challenge.