Extracts and preparations from the tree parasitic plant mistletoe (Viscum album L.) have been used in the treatment of cancer for decades. Numerous preclinical and in vitro studies have reported immunostimulatory, cytotoxic, and proapoptotic effects. Translation of these effects into clinical response continues to pose a problem. While a number of clinical studies have found improvement in quality of life (QOL), data on the efficacy of mistletoe to prolong survival are conflicting and of variable quality. Clinical trial data regarding the toxicity and pharmacokinetics of mistletoe components with known in vitro or preclinical activity are lacking. Mistletoe is a widely used form of complementary and alternative medicine (CAM) for cancer treatment, and research into its use poses the challenges of translation of preclinical data into demonstrable clinical efficacy and investigating CAM approaches as a component of complex cancer treatment systems.