Cancer risk reduction using pharmacological means is an attractive modern preventive approach that supplements the classical behavioural prevention recommendations. Medications that are commonly used by large populations to treat a variety of common, non-cancer-related, medical situations are an attractive candidate pool. This Review discusses three pharmacological agents with the most evidence for their potential as cancer chemopreventive agents: anti-hypercholesterolaemia medications (statins), an antidiabetic agent (metformin) and antiosteoporosis drugs (bisphosphonates). Data are accumulating to support a significant negative association of certain statins with cancer occurrence or survival in several major tumour sites (mostly gastrointestinal tumours and breast cancer), with an augmented combined effect with aspirin or other non-steroidal anti-inflammatory drugs. Metformin, but not other hypoglycaemic drugs, also seems to have some antitumour growth activity, but the amount of evidence in human studies, mainly in breast cancer, is still limited. Experimental and observational data have identified bisphosphonates as a pharmacological group that could have significant impact on incidence and mortality of more than one subsite of malignancy. At the current level of evidence these potential chemopreventive drugs should be considered in high-risk situations or using the personalized approach of maximizing individual benefits and minimizing the potential for adverse effects with the aid of pharmacogenetic indicators.