Implementation of new models of development cooperation have been on the increase coupled with this are calls for the use of horizontal development cooperation mechanisms such as South-South Cooperation (SSC) as a way to enhance aid effectiveness in the health sector of developing countries. In this case series, we review recent experiences in application of SSC initiatives to two public health situations in Africa to demonstrate the veracity of this new paradigm. Our review highlight the immense benefits associated with the use of SSC for health and provide evidence for increasing use of horizontal development coordination mechanisms to strengthen public health services delivery and socioeconomic development among African countries. Opportunities for SSC among African countries include in the areas of disease prevention and control, production of medical products and essential medicines, harmonization of regulatory processes, and health workforce development among others. However, pitfalls such as poor coordination, inadequate political commitment, lack of conducive policy environments, language barrier and inadequate financing opportunities for SSC initiatives present major dilemma for the use of SSC mechanisms. We concludethat the need for a paradigm shift from vertical to horizontal development cooperation needs no further proof but a call to action. We call on the concerned stakeholders to support the establishment of a systematic approach for use of SSC mechanisms in the health sector of Africa, designation of an African Centre of Excellence for SSC in public health and development of a regional mechanism for monitoring and evaluation of SSC initiatives in Africa. Key words: Horizontal development cooperation, South-south cooperation, effective public health services delivery, health system strengthening, aid effectiveness, sustainable development goals, Afric