This chapter addresses the role of neurotrophins in the development of the heart, blood vessels, and neural circuits that control cardiovascular function, as well as the role of neurotrophins in the mature cardiovascular system. The cardiovascular system includes the heart and vasculature whose functions are tightly controlled by the nervous system. Neurons, cardiomyocytes, endothelial cells, vascular smooth muscle cells, and pericytes are all targets for neurotrophin action during development. Neurotrophin expression continues throughout life, and several common pathologies that impact cardiovascular function involve changes in the expression or activity of neurotrophins. These include atherosclerosis, hypertension, diabetes, acute myocardial infarction, and heart failure. In many of these conditions, altered expression of neurotrophins and/or neurotrophin receptors has direct effects on vascular endothelial and smooth muscle cells in addition to effects on nerves that modulate vascular resistance and cardiac function. This chapter summarizes the effects of neurotrophins in cardiovascular physiology and pathophysiology.