Current guidelines recommend statins as first-line therapy for reducing low-density lipoprotein cholesterol (LDL-C) and preventing cardiovascular events. Patients taking statins frequently experience adverse effects during therapy. The first step is to determine whether the adverse effects are indeed related to statin therapy by statin dechallenge and rechallenge. Strategies for managing statin intolerance include changing statins, intermittent dosing, intensification of lifestyle modifications, and using other LDL-C-lowering agents such as ezetimibe, bile acid sequestrants, and LDL apheresis in suitable patients. More controversial approaches include red yeast rice, coenzyme Q10, and vitamin D supplementation. New therapies for LDL-C lowering are in development.