Coenzyme Q10 (CoQ10) is among the most widely used dietary and nutritional supplements on the market. CoQ10 has several fundamental properties that may be beneficial in several clinical situations. This article reviews the pertinent chemical, metabolic, and physiologic properties of CoQ10 and the scientific data and clinical trials that address its use in two common clinical settings: statin-associated myopathy syndrome (SAMS) and congestive heart failure (CHF). Although clinical trials of CoQ10 in SAMS have conflicting conclusions, the weight of the evidence, as seen in meta-analyses, supports the use of CoQ10 in SAMS overall. In CHF, there is a lack of large-scale randomized clinical trial data regarding the use of statins in patients receiving contemporary treatment. However, one relatively recent randomized clinical trial, Q-SYMBIO, suggests an adjunctive role for CoQ10 in CHF. Recommendations regarding the use of CoQ10 in these clinical situations are presented.