In 1948 Haldane first proposed that the high frequencies of thalassaemias in malaria-endemic regions were due to natural selection by malaria. Some of the highest frequencies of alpha+ -thalassaemia are found in the Pacific region of Melanesia. Consequently, Melanesia has provided a unique opportunity for an extensive study of the association between alpha+ -thalassaemia and malaria. Here we review the emergence of alpha+ -thalassaemia in this region and the research that has been carried out, both from the historical perspective and the most recent developments, which may give insight into the selection of alpha+ -thalassaemia by malaria.