The Calophyllum genus (Clusiaceae) is composed of ca. 200 species, with a pantropical distribution. Some species are used as medicinal agents to treat a large number of diseases, including gastric ulcers, infections, pain, tumors, and inflammatory processes, among others. A review of the literature regarding the chemical and biological aspects of these plants indicates cytotoxic activity against several cell lines, inhibition of HIV-1 reverse transcriptase, antisecretory and cytoprotective properties, antinociceptive, molluscicidal and antimicrobial effects, etc., related particularly to the presence of coumarins, xanthones, flavonoids, and triterpenes. This review, therefore, deals with the chemistry, and pharmacology or biology of the main plants belonging to the genus Calophyllum, with particular emphasis on C. brasiliense, studied by our research group.