Glucocorticoid (GC) has important physiological and pharmacological effects, which are mainly mediated by the GC receptor (GR). As a ligand-dependent transcriptional factor, GR activity is regulated by phosphorylation as well as GC; it is subject to hormone-dependent and -independent phosphorylation on several serine and threonine residues, especially in the N terminus. The GR is phosphorylated by cell-specific kinases such as cyclin-dependent kinases (CDKs), glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinases (MAPKs). Phosphorylation regulates signaling and transcriptional activity of GR, thereby modulates the response of cells to GC and may be involved in the development and progression of diseases. Here we reviewed the recent research on GR phosphorylation and its pathophysiological significance.