Multilateral malaria research and control programs in Africa have regained prominence recently as bilateral assistance has diminished. The transnational nature of the threat and the need for inspired leadership, good coordination, and new discoveries to decrease the impact of the disease has led to the founding of the Multilateral Initiative on Malaria, the Roll Back Malaria Project, Global Fund for HIV, Tuberculosis and Malaria (Global Fund), the Medicines for Malaria Venture, and the Malaria Vaccine Initiative, among other groups. Historically, the most striking feature of malaria control and elimination activities was the connectedness and balance between malaria research and control especially, from 1892 to 1949. A combination of scientific originality, perseverance in research, integrated approaches, and social concern were the keys for success. The elimination of Anopheles gambiae from Upper Egypt in 1942 using integrated vector control methods is a prime example of malaria control during the first half of the 20th century where those factors were brought together. After 1949, there were three decades of great optimism. Four notable landmarks characterized this period: the Kampala Conference in 1950; the Global Malaria Eradication Program beginning in 1955; the primary health care strategies adopted by most African States after attaining their political independence in the 1960s, and accelerating in the 1980s; and creation of the Special Program in Training and Research in Tropical Diseases at the World Health Organization in 1975. The initial highly encouraging operational results, largely obtained in temperate or subtropical areas where transmission was unstable, engendered undue expectations for the success of identical antimalarial measures elsewhere. Many were convinced that the eradication was in sight, such that support for malaria research virtually ceased. Young, bright scientists were discouraged from seeking a career in a discipline that appeared to soon become superfluous. It took more than three decades to modify antimalarial strategies and to rehabilitate long-term control as an intermediate objective. In Africa, although multilateral malaria programs have grown over the past half century and proved the most successful, fragmentation of co-ordination remains and is a major challenge. The proliferation of malaria programs in the late 1990s has brought substantial additional funds and expertise. However, excessive funding competition and failure of different programs to collaborate has resulted in poor communication and duplication of activities. The capacities of the African nations to conduct high-quality research and to coordinate control efforts are in great jeopardy. There is an urgent need for a non-partisan umbrella organ to coordinate and facilitate the network of alliances and programs in malaria research and control in Africa.