A small but significant link between new-onset diabetes mellitus (NOD) and statin therapy was noted with rosuvastatin users in the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin study. Since then multiple analyses have further confirmed this association, with most studies demonstrating a modest increase in NOD with statin therapy, especially among individuals with risk factors for developing diabetes mellitus. More recent observational analyses suggest a stronger correlation between statin use and NOD, however. A definitive mechanism confirming causation between statins and glucose impairment remains elusive, but many have been proposed. Although considered a class effect by the US Food and Drug Administration, most data indicate NOD is dependent upon the dose and potency of the statin, with certain agents appearing to be less diabetogenic. The consensus is that the benefits of statin therapy far outweigh the risk of NOD, especially among patients with high cardiovascular risk. Nonetheless, more studies are needed to better understand this association and long-term clinical implications. In the meantime, we provide clinicians with a practical guide to assist with clinical decision making when prescribing statin therapy. Overall, this article serves to provide the primary care physician with a timely review of the most clinically relevant data regarding statins and NOD, with hopes to ultimately optimize statin prescribing and limit any potential drug-induced glucose impairment.