High mobility group box-1 (HMGB1) is a highly conserved, ubiquitous protein in the nuclei and cytoplasm of almost all cells. After binding to its receptor, HMGB1, which is derived from necrotic cells and activated macrophages/monocytes, functions as a critical mediator of inflammation and promotes tissue repair and regeneration. Many recent studies demonstrated that HMGB1 played a pivotal role in cardiovascular diseases, such as atherosclerosis, myocardial ischemia/reperfusion injury, heart failure, and myocardial infarction. In this review, we focus on HMGB1 and summarize the association of HMGB1 with cardiovascular diseases.