Rosuvastatin (Crestor®) is an HMG-CoA reductase inhibitor (statin) that has both lipid-lowering and anti-inflammatory effects. The drug has various indications in the US, including the primary prevention of cardiovascular disease (CVD) in patients with no clinical evidence of coronary heart disease who are at increased risk of CVD based on their age, a high-sensitivity C-reactive protein (hsCRP) level of ≥2 mg/L, and at least one other CVD risk factor. The efficacy of rosuvastatin in apparently healthy women (aged ≥60 years) or men (aged ≥50 years) with normal low-density lipoprotein cholesterol (LDL-C) levels and elevated hsCRP levels was demonstrated in the large, randomized, double-blind, multinational, JUPITER trial. Relative to placebo, rosuvastatin 20 mg once daily for a median follow-up of 1.9 years significantly reduced the occurrence of first major cardiovascular events in this trial (primary endpoint). A between-group difference in favor of rosuvastatin was also demonstrated for various other endpoints, including overall deaths and the nonatherothrombotic endpoint of venous thromboembolism. Rosuvastatin remained more effective than placebo when primary endpoint results were stratified according to various baseline factors, including in patient subgroups thought to be at low risk of CVD. In addition, rosuvastatin was associated with reductions in LDL-C and hsCRP levels, and these reductions appeared to occur independently of each other. The greatest clinical benefit was observed in rosuvastatin recipients achieving an LDL-C level of <1.8 mmol/L (<70 mg/dL) and an hsCRP level of <2 mg/L or, even more so, <1 mg/L. Rosuvastatin was well tolerated in the JUPITER trial, with most adverse events being mild to moderate in severity. Myalgia, arthralgia, constipation, and nausea were the most commonly occurring treatment-related adverse events, and the incidence of monitored adverse events and laboratory measurements was generally similar in the rosuvastatin and placebo groups. It is not yet known whether the mechanism of benefit of rosuvastatin is via lipid effects, anti-inflammatory effects, or a mixture of both, and the use of rosuvastatin solely on the basis of elevated hsCRP levels is controversial. Nonetheless, the drug remains an important pharmacologic option in the prevention of CVD, and has demonstrated efficacy in preventing major cardiovascular events in apparently healthy women (aged ≥60 years) or men (aged ≥50 years) with normal LDL-C levels and elevated hsCRP levels.