The beneficial role of statins in primary and secondary prevention of coronary heart disease has resulted in their frequent use in clinical practice. However, safety concerns, especially regarding hepatotoxicity, have driven multiple trials, which have demonstrated the low incidence of statin-related hepatic adverse effects. The most commonly reported hepatic adverse effect is the phenomenon known as transaminitis, in which liver enzyme levels are elevated in the absence of proven hepatotoxicity. This class effect is usually asymptomatic, reversible, and dose-related. However, the increasing incidence of chronic liver diseases, including nonalcoholic fatty liver disease and hepatitis C, has created a new challenge when initiating statin treatment in patients with high cardiovascular risk. These diseases result in abnormally high liver biochemistry values, discouraging statin use by clinicians, fostering treatment discontinuation, and leaving a large number of at-risk patients untreated. A PubMed/MEDLINE search of the literature regarding statin safety (January 1, 1994-December 31, 2008) was performed, using the following search terms: statin safety, statin-related hepatotoxicity, and chronic liver disease and statin use, as well as the specific names of different statins and different liver diseases. Relevant clinical trials, review articles, panel discussions, and guideline recommendations were selected. This review supports the use of statin treatment in patients with high cardiovascular risk whose elevated aminotransferase levels have no clinical relevance or are attributable to known stable chronic liver conditions. For each patient, the decision should be based on an individual assessment of risks and benefits.