The launch of the Mectizan Donation Program (MDP) in 1987, by Merck & Co., Inc., created a number of new opportunities for onchocerciasis control. The microfilaricide Mectizan was rapidly put to ?use by the Onchocerciasis Control Programme in West Africa (OCP), for mass treatment by field teams in selected areas. Other milestones in Mectizan treatment included the establishment, in 1992, of the Onchocerciasis Elimination Program for the Americas, and the creation of the African Programme for Onchocerciasis Control (APOC) in 1995, the latter programme covering all African countries in need outside of the OCP area. In 1998, the donation of Mectizan was expanded to include the treatment of lymphatic filariasis in those African countries where that disease is co-endemic with onchocerciasis. In the past, the development of a broad partnership around the MDP played a very important role, including non-governmental development organizations collaborating with the ministries of health in endemic countries. A new community-directed treatment strategy, which made it easier to reach out to all those in need, including those in remote areas, was developed by the APOC in collaboration with the World Health Organization's Special Programme for Research and Training in Tropical Diseases (TDR). Several drug-management issues, including dosing, shelf-life, safety, and the reporting of severe adverse experiences, were addressed by the MDP, through its Mectizan Expert Committee, and by Merck & Co., Inc. A major research effort for the safe treatment of onchocerciasis in loiasis-endemic areas has also been supported by the MDP. Presently there are national programmes for Mectizan mass treatment in all 33 endemic countries in need of such treatment; >69 million Mectizan treatments for onchocerciasis were provided during 2006, and this number is expected to grow to at least 100 million treatments/year by 2010. This achievement has resulted in great public-health and socio-economic benefits for the populations concerned. Future challenges will include additional support to 'fragile states' resulting from conflicts or natural disasters, and the need for a strengthened primary healthcare (PHC) infrastructure. The community-directed-treatment approach has been a great success but there is still a need to link the treatments to PHC, for the long-term sustainability of the treatments. The presence of loiasis in vast areas of Central Africa imposes a need for the mapping of that disease, and the application of safety precautions when distributing Mectizan in those areas. The recent decision to extend the APOC up to 2015 should facilitate the building of sustainable Mectizan treatment programmes that are integrated with the control of other neglected tropical diseases, such as lymphatic filariasis, intestinal helminths and trachoma. It will be important to define the safe end-point for Mectizan treatment in various settings, and an ongoing study by TDR will address this issue. There is also a need to consider the application of more frequent Mectizan treatments, possibly with adjunct measures, such as ground-based vector control in selected areas, or new chemotherapeutic approaches (as and when they become available).