Guggulsterone (GS) is a phytosterol derived from the gum resin of guggul plants that have been used traditionally to treat various disorders such as burns, wounds, gastric ulcer, cough, gum diseases, urinary complaints, diarrhea, stomach cramps, fascioliasis, and intestinal worms. It has anti-inflammatory and antioxidative properties and has recently attracted substantial attention due to its cancer chemopreventive and therapeutic potential exemplified by its antiproliferative, antimetastatic, and proapoptotic properties in many cancer cell lines and animal models. This review highlights some of the cancer chemopreventive/therapeutic targets of GS and the underlying molecular mechanisms.