Milk thistle (Silybum marianum) is an herb that is increasingly used in oncology research and treatment settings. Historically, it has been used to treat liver and biliary disorders and has been used in detoxification and cleansing protocols. However, milk thistle is increasingly being investigated for its use in adult and pediatric populations for oncology indications. Possible indications during cancer treatment include cleansing and detoxification after chemotherapy, preventing hepatotoxicity during chemotherapy, treating hepatotoxicity after chemotherapy, and potentiating chemotherapy and radiation therapy as an adjunctive treatment. Milk thistle may also have applications in ameliorating long-term hepatic and cardiovascular effects of cancer treatment. Preliminary studies are investigating its use as a chemopreventive agent and possibly to treat cancer directly. Much of milk thistle's current clinical use grows out of historical uses but is informed by an increasing number of clinical trials and animal studies. This article provides an overview of the current clinical applications of milk thistle in the oncology setting, including guidelines on commonly used forms and doses.