Abstract: G protein-coupled receptor kinase 2 (GRK2) is a kinase capable of desensitizing multiple G protein-coupled receptors (GPCRs). Myocardial GRK2 can inhibit the functions of β-adrenergic receptor (β-ARs), a member of GPCRs, terminating its G-protein-mediated signaling by cAMP and attenuating myocardial cell contractility and adrenergic reserve. Blocking GRK2 restores the sensitivity of β-ARs, which in turn improves and reverses heart failure after myocardial infarction. In recent years, the non-classical effects of GRK2 in cardiovascular disease have also been elucidated, including the negative regulation of insulin signaling, mitochondrial regulation, and modification of cardiomyocyte survival and apoptosis signals. These new effects suggest that GRK2 may not be dependent on its typical GPCR. Desensitization affects cardiac contractile function, cellular metabolism and survival, and promotes heart failure. This article aims to review and summarize the latest research progress in the relationship between GRK2 and myocardial fibrosis at home and abroad.