β-blockers are a class of drugs that are widely used in treating cardiac, respiratory and other ailments. They act by blocking β-adrenergic receptor-mediated signaling. Studies in various cancers have shown that patients taking a β-blocker have higher survival and lower recurrence and metastasis rates. This is supported by several preclinical and in vitro studies showing that adrenergic activation modulates apoptosis, promotes angiogenesis and other cancer hallmarks, and these effects can be abrogated by β-blockers. These studies provide a rationale for the use of β-blockers as adjuvants with cancer chemotherapy. However, all published studies so far are retrospective and most do not take into account the specific β-blocker used or address which is most likely to benefit cancer patients. The published epidemiological studies are correlative and have not examined the adrenergic receptor status of the tumors. Knowledge of the β-adrenergic receptor status of tumor cells is essential in choosing the best β-blocker for adjuvant therapy. A comprehensive, prospective study is necessary to definitively prove the utility of using β-blockers with chemotherapy and to identify the specific β-blocker most likely to benefit patients with cancer.