Statins are widely used for their cholesterol-lowering properties and proven reduction of cardiovascular disease risk. Many patients take statins as long-term treatment for a variety of conditions without a clear-cut understanding of how treatment duration affects the frequency of adverse effects. We aimed to evaluate whether the frequencies of documented adverse events increase, decrease, or remain unchanged with long-term statin use. We reviewed the established literature to define the currently known adverse effects of statin therapy, including myopathy, central nervous system effects, and the appearance of diabetes, and the frequency of these events with long-term medication use. The frequency of adverse effects associated with long-term statin therapy appears to be low. Many patients who develop side effects from statin therapy do so relatively soon after initiation of therapy, so the frequency of side effects from statin therapy when expressed as a percentage of current users decreases over time. Nevertheless, patients may develop side effects such as muscle pain and weakness years after starting statin therapy; however, the absolute number of patients affected by statin myopathy increases with treatment duration. Also, clinical trials of statin therapy rarely exceed 5 years, so it is impossible to determine with certainty the frequency of long-term side effects with these drugs.