For millions of years, invertebrates and malaria parasites have coexisted and to date, malaria remains the most important human parasitic disease. This co-evolution had profound impacts on the movements of early hominids and on the genome of modern humans. Over the past two centuries, progress has been made with the discovery of the parasite, its transmission, and medicines, paving the way to the control of the disease and its elimination in some countries. However, the Plasmodium parasite is a formidable foe capable of developing resistance to drugs, and the mosquito vector has adapted to insecticides, foiling all attempts to eradicate the disease. Over recent years the economic and social costs of malaria have been recognized and more funds have been mobilized than ever before, however further efforts are needed. National programs, international institutions and researchers will need to do better if the preventable deaths of hundreds of thousands of mostly African children are to be averted.