3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are extremely well tolerated but are associated with a range of mild-to-moderate statin-associated muscle symptoms (SAMS). Estimates of SAMS incidence vary from <1% in industry-funded clinical trials to 10-25% in nonindustry-funded clinical trials and ∼60% in some observational studies. SAMS are important because they result in dose reduction or discontinuation of these life-saving medications, accompanied by higher healthcare costs and cardiac events. The mechanisms that produce SAMS are not clearly defined. Statins block the production of farnesyl pyrophosphate, an intermediate in the mevalonate pathway, which is responsible for the production of coenzyme Q10 (CoQ10). This knowledge has prompted the hypothesis that reductions in plasma CoQ10 concentrations contribute to SAMS. Consequently, CoQ10 is popular as a form of adjuvant therapy for the treatment of SAMS. However, the data evaluating the efficacy of CoQ10 supplementation has been equivocal, with some, but not all, studies suggesting that CoQ10 supplementation mitigates muscular complaints. This review discusses the rationale for using CoQ10 in SAMS, the results of CoQ10 clinical trials, the suggested management of SAMS, and the lessons learned about CoQ10 treatment of this problem.