Cardiovascular diseases claim more lives worldwide than any other. Etiologically, the dominant trajectory involves atherosclerosis, a chronic inflammatory process of lipid-rich lesion growth in the vascular wall that can cause life-threatening myocardial infarction (MI). Those who survive MI can develop congestive heart failure, a chronic condition of inadequate pump activity that is frequently fatal. Leukocytes (white blood cells) are important participants at the various stages of cardiovascular disease progression and complication. This Review will discuss leukocyte function in atherosclerosis, MI, and heart failure.