Silymarin (Silybum marianum [L.] Gaertn. [Asteraceae]) is a promising agent for cancer prevention, adjuvant cancer treatment, and reduction of iatrogenic toxicity. Although it is safe and free of serious adverse side effects, few studies have evaluated its use alongside conventional cytotoxic therapies, and adverse events associated with long-term administration are uncertain. Although it may prevent some types of cancer, its promotion of tissue regeneration and its potential estrogen activity could promote the growth of some tumors. Further clinical trials using authenticated fractions of silymarin as simple and complex derivatives are required prior to any general recommendations. Future research should focus on authentication of active chemicals, pharmacokinetics, adverse interactions and quality control, prevention of cancer initiation and progression, adjuvant therapy for specific cancers, and prevention of toxicity from anticancer therapies.