The parathyroid hormone-related peptide (PTHrP) was initially identified in the early eighties, as the humoral mediator causing hypercalcaemia associated with malignancy. However, recently PTHrP was also shown to mediate a wide range of local paracrine/autocrine and intracrine functions in various tissues under physiological and pathological conditions. Indeed, PTHrP is a polyhormone, which can act through different receptors, including the type 1 parathyroid hormone (PTH) receptor 1 (PTH-1R). In the cardiovascular system, PTHrP appears to have potent effects on vascular smooth muscle cells and cardiomyocytes, where it participates in different pathological conditions, such as ischemia and heart failure. Therefore, it is conceivable that further studies on the regulation of PTHrP expression, characterization of its autocrine/paracrine/intracrine functions and definition of its intracellular signal transduction pathways in cardiomyocytes and cardiac vascular smooth muscle cells can elucidate the potential role of PTHrP in cardiovascular pathophysiology.