There is growing interest in the notion that perioperative factors may influence the long-term outcome of cancer surgery. Among these factors, pharmacologic agents including anesthetics and analgesics have been scrutinized for their potential effect on tumors. Opioids are particularly interesting in this context, as conflicting literature reports both pro- and anti-tumor effects for this class of drugs in every aspect of tumor growth and metastasis that has been examined. Cancer and non-cancer cells important to the tumor biology may be affected, as demonstrated using a variety of in vitro and preclinical models. More evidence is required to optimize the perioperative pain management of cancer surgery patients.