The field of intracrine physiology attempts to codify the biological actions of intracrines--extracellular signaling proteins or peptides that also operate in the intracellular space, either because they are retained in their cells of synthesis or because they have been internalized by a target cell. Intracrines are structurally diverse; hormones, growth factors, DNA-binding proteins and enzymes can all display intracrine functionality. Here, we review the role of intracrines in the heart and vasculature, including the intracrine actions of renin-angiotensin-system components in cardiac pathology, dynorphin B in cardiac development, and a variety of factors in pathologic and therapeutic angiogenesis. We argue that principles of intracrine physiology can inform our understanding of important pathologic processes such as left ventricular hypertrophy, diabetic cardiomyopathy and arrythmogenesis, and can aid the development of more-effective therapeutic interventions in cardiovascular disease.