Purpose of Review <p>Outcome benefits for HMG-CoA reductase inhibitor (statin) use in the prevention of atherosclerotic cardiovascular disease (ASCVD) are well established and yet, statins remain underutilized with only half of eligible individuals receiving them among certain vulnerable populations. This review critically examines available data to provide a summary of the current evidence for statin use in select populations.</p> Recent findings <p>Lipid management can be more complex in patients with chronic kidney disease (CKD), organ transplants, metabolic dysfunction associated with steatotic liver disease (MASLD), and human immunodeficiency virus (HIV). Statins are generally safe and effective to reduce the burden of ASCVD among these highly heterogeneous groups of patients and should be considered with careful attention to their concomitant disease state. Herein, we focus on appropriate statin use in these challenging to treat conditions, their relationship with increased ASCVD risk, and approaches to statin use for ASCVD risk reduction.</p> Summary <p>Although further research is needed to define optimal therapy in select high risk groups for ASCVD prevention, statins are proven to be clinically efficacious, safe, and cost-effective for ASCVD prevention, warranting greater efforts to increase their use.</p> Graphical Abstract <p></p>