More than four decades passed since sigma receptors were first mentioned. Since then, existence of at least two receptor subtypes and their tissue distributions have been proposed. Nowadays, it is clear, that sigma receptors are unique ubiquitous proteins with pluripotent function, which can interact with so many different classes of proteins. As the endoplasmic resident proteins, they work as molecular chaperones – accompany various proteins during their folding, ensure trafficking of the maturated proteins between cellular organelles and regulate their functions. In the heart, sigma receptor type 1 is more dominant. Cardiac sigma 1 receptors regulate response to endoplasmic reticulum stress, modulates calcium signaling in cardiomyocyte and can affect function of voltage-gated ion channels. They contributed in pathophysiology of cardiac hypertrophy, heart failure and many other cardiovascular disorders. Therefore, sigma receptors are potential novel targets for specific treatment of cardiovascular diseases.