Concern regarding the safety of continuing statins in critically ill patients is logical because statins have demonstrated risk for harm in noncritically ill patients. Postmarketing reports have demonstrated risk of statin-induced myopathy and less often, severe liver injury, even in noncritically ill patients.11,12 Risk for myopathy appears greatest with higher-dose simvastatin and correlates with serum concentrations of the statin.11,13 Risk for potentially toxic serum levels is particularly increased in the 15% of the population that carries certain variants of the SLCO1B1 gene, which encodes the organic anion transporter polypeptides responsible for hepatocyte uptake of statins.13 Two studies examining the pharmacokinetics of statins in critically ill patients demonstrated that despite statin administration at normal doses, serum drug levels often become supratherapeutic.14,15 The authors surmised that increased serum statin concentrations in these critically ill patients were related to frequent concomitant use of other medications that affect cytochrome P450 metabolism, such as azoles, haloperidol, midazolam, and amiodarone. Of interest, the ARDSNet study Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome found that the median peak plasma level of rosuvastatin was actually below the intended target range.8 Rosuvastatin has less cytochrome P450 interaction than simvastatin or atorvastatin, and this likely explains the increased risk for toxic statin levels in patients taking the latter two drugs. Despite using a statin with less risk for myopathy and measuring lower-than-anticipated plasma levels, rosuvastatin treatment raised concern for toxicity because patients on treatment had significantly higher aspartate aminotransferase levels and fewer days free of hepatic and renal failure. Of the 109 patients in this study who were taking a statin prior to enrollment, continuation of a statin rather than placebo resulted in a nonstatistically significant 11% absolute increase in risk of death at 90 days. Although this study was not powered to specifically evaluate mortality in patients with sepsis on a prior statin, it raises concern that continuation may actually cause more harm than was previously recognized.