The circulatory system provides the tissues of the body with oxygen and nutrients for survival, allows for the dissemination of inflammatory cells, and clears metabolic waste from building up and damaging tissue. Atherosclerotic disease, the build-up of fat, inflammatory cells, and fibrotic tissue in the vessel wall, hinders this function, resulting in inadequate perfusion of the target tissue. Hypoxia, or lack of oxygen, rapidly results in cellular dysfunction that profoundly affects the functionality of the overall tissue. Atherosclerosis-associated tissue ischemia and hypoxia because of loss of blood flow underlies several significant disease pathologies including ischemic heart disease, stroke, and peripheral artery disease. In this eBook, we examine the process of atherosclerotic plaque formation both at the cellular level and the level of clinical presentation. Through this book, we hope to impart to the reader a better understanding of how vessel structure, environmental risk factors, and genetic predisposition contribute to atherosclerotic disease and how current and future therapies seek to circumvent the cellular processes contributing to plaque formation to reduce atherosclerotic plaque burden and clinical complications.