Hepatocystis parasites are the closest relatives of Plasmodium species of mammals. They infect monkeys, bats, squirrels, and ungulates in Africa, Asia, and Australia. A prevalence of up to 100% has been documented in fruit bats and monkeys. Twenty-five morphospecies have been described, and cross-species transmission, divergent Hepatocystis lineages, and species complexes are reported in primate and bat hosts. Biting midges (Culicoides) are the only known vectors. In the vertebrate, merogony occurs exclusively in the liver, resulting in formation of macroscopic merocysts. Merozoites invade erythrocytes and transform directly into sexual gametocytes, thereby omitting asexual replication and associated health conditions. Gametocytes can persist for several weeks and fertilize after a bloodmeal in the Culicoides midgut. The Hepatocystis genome features unique gene families, a low number of Plasmodium interspersed repeat (pir) genes, and an absence of the reticulocyte-binding protein family.