CD36 is a multiligand receptor associated with a broad array of physiological processes and involved in markedly diverse disorders, including atherosclerosis, insulin resistance and diabetes, dyslipidemia, tumor angiogenesis, and host defense against Plasmodium falciparum. CD36 deficiency has proved to be common, particularly in ethnic groups such as African Americans and Asians. CD36 is commonly expressed on blasts in acute monocytic leukemia, megakaryoblastic leukemia, and erythroleukemia. The role of CD36 in sickle cell crises and cerebral malaria is debatable. As a receptor for thrombospondin 1, CD36 plays a role in the regulation of angiogenesis, which may be a therapeutic strategy for controlling the dissemination of malignant neoplasms. The future challenge will be to further understand the mechanisms by which CD36 affects these diverse functions and to design therapeutic strategies that can alter the course of the diseases.