Statins are a class of drugs registered and prescribed to lower total and LDL-cholesterol. Clinical trials performed in the last 25 years have shown that these agents are effective in improving cardiovascular out- comes in several different clinical settings. However, in some cases statin treatment may be associated with significant side effects and adverse reactions. The occurrence of such adverse events during statin therapy may cause discontinuation of treatment together with the impossibility of achieving recommended lipid goals. The clinical condition in which patients experience major unacceptable symptoms and/or develop laboratory abnormalities during statin therapy is defined as statin intolerance. This document outlines the diagnostic and therapeutic pathways for the clinical management of patients with hypercholesterolemia and statin intolerance.