Histamine is a biogenic amine involved in various pathophysiological processes, such as regulation of immune responses and anaphylactic reaction, neural signal transduction, secretion of gastric acid and hematopoiesis. The effects of histamine is dependent on its binding 4 subtypes of histamine receptors (HR), activating different intracellular pathways. Inflammation and immune responses play an important role in multiple cardiovascular disease, including coronary artery diseases, heart failure, myocarditis and pericarditis. The complex regulatory interaction between histamine and immune responses are receiving more and more attention. In this review, we will discuss the effects of histamine in innate immune responses and cardiovascular diseases.