In this chapter, the current knowledge of the phytochemistry and pharmacology of Cerbera odollam and Cerbera manghas is updated with a description of their botany and uses. These two closely related coastal tree species are mangrove associates with overlapping geographical distribution, centered in Southeast Asia. Flowers are trumpet-shaped and white with those of C. odollam having a yellow eye and those of C. manghas having a red eye. Cerbera fruits are oval with those of C. manghas slightly elongated, resembling fruits of mango. The chemical constituents of Cerbera species include cardiac glycosides, terpenoids, phenolic acids, lignans, iridoids, flavonoids, and sterols. Cardiac glycosides are cardenolides with their chemical structures having a steroid nucleus, lactone moiety, and sugar component. Cardenolides, such as cerberin, dehydrocerberin, tanghinin, deacetyltanghinin, tanghinigenin, and neriifolin, have promising anticancer activities and other pharmacological properties. Endophytic fungi have been isolated from C. manghas and they contain secondary metabolites that have medical, industrial, or environmental prospects. However, most of these cardenolides are also cardiotoxic. Cerbera poisoning is intentional (suicidal) or accidental (transmitted). The latter occurs via the consumption of coconut crab (Birgus latro). Cerbera species possess cardiac glycosides, which have anticancer and other pharmacological properties, but they are also lethally toxic. In the conclusion, projects for further research are recommended.