The species of genus Calophyllum have been reported for several ethnomedicinal uses in the traditional systems of medicine. The scientific study of the genus Calophyllum revealed that it is a rich source of bioactive secondary metabolites. These phytochemicals have shown a wide range of biological activities. Some of these have reached to the clinical developmental stage. The Calophyllum inophyllum seed oil has been proved to be an acceptable sustainable source of biodiesel. Few species of the genus are endangered and have been included in the red list of threatened species by the IUCN Red List. Owing to the importance of the genus a review of its ethnomedicinal uses, phytochemistry, and pharmacology has been carried out. It will further help to explore the molecular mechanism of phytochemicals for health benefits.