Atherosclerosis is a disease of the cardiovascular system and its clinical manifestations account for a considerable portion of deaths worldwide. While pathogenesis is initiated by defects in the arterial vasculature and in lipoprotein metabolism, the accompanying sterile inflammation is a fundamental aspect of disease progression. Over the course of the last 15 years, a vast body of evidence on inflammatory triggers, receptors, and effector programs in the context of atherosclerosis has accumulated. This chapter aims to give an overview of the sterile inflammatory processes that drive atherogenesis, focusing on how the innate immune system senses homeostatic imbalance during disease progression. Furthermore, we will illustrate how pharmacological agents and dietary factors can modulate inflammation in atherosclerosis.