With increasing knowledge of the regulatory mechanisms of G-protein-coupled receptor signaling in heart physiology, many studies have focused on the role of this system in cardiovascular disease. In recent years, scientists have moved their attention from the receptors to their regulatory proteins: the G-protein-coupled receptor kinases. This class of protein is indispensable for terminating signaling of G-protein-coupled receptors through receptor desensitization and downregulation. This article attempts to assemble the currently available information regarding G-protein-coupled receptor kinases and their role in cardiovascular disease and, in particular, the potential employment of G-protein-coupled receptor kinase 2 as biomarker of cardiac dysfunction.