Statins remain the cornerstone of lipid-lowering treatment. They significantly reducing cardiovascular morbidity and mortality in primary and secondary prevention settings. Statin-treated patients may present adverse events (clinical and/or biochemical) that can lead to treatment discontinuation or a reduction in the dose of statins. Statin intolerance may appear at any time during the treatment. In each case, secondary causes should be assessed and treated and lifestyle measures should be implemented. Up to 3 different statins can be tried at a low dose; statin dosing everyother- day or once weekly may be another option. Several non-statin lipid-lowering drugs (ezetimibe, fibrates, colesevelam, niacin or proprotein convertase subtilisin kexin-9 inhibitors) are available as monotherapy or in combination with statins to achieve efficacy and tolerability.