The 2013 ACC/AHA guidelines on blood cholesterol management were a major shift in the delineation of the main patient groups that could benefit from statin therapy and emphasized the use of higher-intensity statin therapies. In 2016, an expert consensus panel from the ACC recommended the use of nonstatin therapies (ezetimibe and PCSK9 inhibitors) in addition to maximally tolerated statin therapy in individuals whose LDL-cholesterol and non-HDL-cholesterol levels remained above certain thresholds after statin treatment. Given the substantial benefits of statin therapies in both primary and secondary prevention of cardiovascular disease, their long-term safety has become a concern. The potential harmful effects of statin therapy on muscle and liver have been known for some time, but new concerns have emerged regarding the risk of new-onset diabetes mellitus, cognitive impairment and haemorrhagic stroke associated with the use of statins and the risks of achieving very low levels of LDL cholesterol. The increased media attention on the adverse events associated with statins has unfortunately led to statin therapy discontinuation, nonadherence to therapy or concerns about initiating statin therapy. In this Review, we explore the safety of statin therapy in light of the latest evidence and provide clinicians with reassurance about the safety of statins. Overwhelming evidence suggests that the benefits of statin therapy far outweigh any real or perceived risks.