As the clinical applications of immune checkpoint inhibitors (ICIs) expand, our knowledge of the potential adverse effects of these drugs continues to broaden. Emerging evidence supports the association between ICI therapy with accelerated atherosclerosis and atherosclerotic cardiovascular (CV) events. We discuss the biological plausibility and the clinical evidence supporting an effect of inhibition of these immune checkpoints on atherosclerotic CV disease. Further, we provide a perspective on potential diagnostic and pharmacological strategies to reduce atherosclerotic risk in ICI-treated patients. Our understanding of the pathophysiology of ICI-related atherosclerosis is in its early stages. Further research is needed to identify the mechanisms linking ICI therapy to atherosclerosis, leverage the insight that ICI therapy provides into CV biology, and develop robust approaches to manage the expanding cohort of patients who may be at risk for atherosclerotic CV disease.