AbstractStilbene is an abundant structural scaffold in nature, and stilbene‐based compounds have been widely reported for their biological activity. Notably, (E)‐resveratrol and its natural stilbene‐containing derivatives have been extensively investigated as cardioprotective, potent antioxidant, anti‐inflammatory, and anticancer agents. Starting from its potent chemotherapeutic activity against a wide variety of cancers, the stilbene scaffold has been subject to synthetic manipulations with the aim of obtaining new analogues with improved anticancer activity and better bioavailability. Within the last decade, the majority of new synthetic stilbene derivatives have demonstrated significant anticancer activity against a large number of cancer cell lines, depending on the type and position of substituents on the stilbene skeleton. This review focuses on the structure–activity relationship of the key compounds containing a stilbene scaffold and describes how the structural modifications affect their anticancer activity.