Despite the significant contributions of the various North-South research partnerships during the past five decades to enhancing research capacity in the South, they have faced a number of challenges associated with the various partnerships. There have been limited attempts to critically examine the successes and challenges associated with these partnerships. Based on the experiences of implementing the 'HIV Prevention for Rural Youth' programme by a Canadian-Nigerian partnership during a four year period, this paper outlines the successes achieved and the challenges faced. The paper reviews the context of contemporary North-South research collaboration which provided the framework for the implementation of the HIV Prevention for Rural Youth. It then examines the benefits which the implementation of the programme have stimulated as well as the various challenges which confronted the partnership and how they were handled. The implications of the project's implementation experiences for future North-South collaborative research programmes are highlighted.