Nature is an inexhaustible source of natural compounds with interesting biological activities. Ingeneral, natural products are an important source of new compounds with a variety of structural arrangementsand singular properties. Styryl lactones are a group of secondary metabolites ubiquitous in the genusGoniothalamus that have demonstrated to possess interesting biological properties, in particularantiproliferative activity against cancer cells. In general, the cytotoxicity of styryl lactones appears to bespecific against cancer cells since insignificant effects of these compounds on normal cells are reported. Alarge body of evidence suggests that the antiproliferative activity of styryl lactones is associated with theinduction of apoptosis in target cells. In the first part of this review we discuss the biological activities ofstyryl lactones focusing on cancer cells, the causal agent of Chagas disease and the vectors for yellow feverand human lymphatic filariasis. Structure-activity relationship s are described in detail for ninety styryllactones. The last part describes the molecular targets of styryl lactones for inducing apoptosis, as well asimmunosuppressive and inflammatory processes. Overall, understanding how these compounds exert theiractivities in biological system is essential for future development and application of styryl lactones forhuman health.