G protein-coupled receptors (GPCRs) play key roles in cell signal transduction. GPCR structures are important for understanding structure-functional relationship of the GPCR superfamily. Before the year 2000, the high-resolution GPCR structure is one of the major obstacles in structural biology field. In recent years, the structural studies of GPCRs have been developed remarkably. Here, we briefly summarize the methods used in GPCR structure determination, and also take the CCR5 and P2Y1R structures as examples to discuss the significance of GPCR structures on functional studies and drug discovery.