OBJECTIVE Preclinical studies have elucidated molecular pathways by which specific classes of antihypertensive agents may promote, or protect, against tumor development and progression. Observational studies have proposed an association between antihypertensive agents and cancer, but due to limitations inherent to their study design cannot alone establish causality. Moreover, prospective randomized clinical trials (RCT) of antihypertensive agents have focused on cardiovascular and renal outcomes, rather than incidence of new cancer, making inference from RCTs problematic. The purpose of this review was to highlight the classes of medications implicated in increased cancer risk, with a focus on angiotensin receptor blocker (ARB) therapy, as recent published data surrounding their use remains the most controversial. RESULTS A recent meta-analysis of RCTs found a significant increase in the risk of cancer with ARBs when compared with control, eliciting a safety review by the Food and Drug Administration. Subsequently, more robust meta-analyses have refuted these findings, demonstrating no association between any of the currently used antihypertensive agents and cancer. Despite the complex methodology of these meta-analyses, the randomized trials used for analysis are fraught with inconsistencies, including the availability of cancer outcomes, a brief time to follow-up as compared with the latency of cancer, and heterogeneous use of antihypertensive agents. CONCLUSIONS The medical literature has long hypothesized potentially carcinogenic effects of antihypertensive agents, but to date there is no convincing evidence that any of the individual antihypertensives in clinical use, at the dosages and duration tested, lead to higher rates of cancer.