The article provides an overview of the recent advancements in the structural and functional understanding of G protein-coupled receptors (GPCRs). Over the past few years, crystallography has led to the determination of structures for 14 distinct GPCRs, with seven of them published in 2012 alone. These structures, including those of adrenergic, rhodopsin, and adenosine receptor systems, have provided insights into the dynamic equilibrium between different functional states of GPCRs. Biochemical and biophysical techniques, such as NMR and HDX-MS, have complemented these structural studies by revealing ligand-dependent dynamic changes in receptor conformations. High-resolution structures, such as the 1.8 Å adenosine A2a receptor, have highlighted the allosteric nature of GPCRs, which are influenced by factors like sodium, lipids, cholesterol, and water. This wealth of data has helped redefine our understanding of how GPCRs recognize diverse ligands and transmit signals across the cell membrane, as well as the structural basis for allosteric modulation and biased signaling. The article also discusses the structural diversity within GPCR subfamilies and the comprehensive structural coverage of the opioid subfamily, emphasizing the conserved microswitches and ligand-dependent triggers that control receptor activation. Additionally, it explores the structural framework for GPCR activation, the role of G protein binding and signaling, and the insights into allosteric modulation and oligomerization. Finally, the article highlights the importance of complementary biophysical studies in understanding GPCR conformational dynamics and the potential for using "biased" and allosteric ligands to modulate receptor function.The article provides an overview of the recent advancements in the structural and functional understanding of G protein-coupled receptors (GPCRs). Over the past few years, crystallography has led to the determination of structures for 14 distinct GPCRs, with seven of them published in 2012 alone. These structures, including those of adrenergic, rhodopsin, and adenosine receptor systems, have provided insights into the dynamic equilibrium between different functional states of GPCRs. Biochemical and biophysical techniques, such as NMR and HDX-MS, have complemented these structural studies by revealing ligand-dependent dynamic changes in receptor conformations. High-resolution structures, such as the 1.8 Å adenosine A2a receptor, have highlighted the allosteric nature of GPCRs, which are influenced by factors like sodium, lipids, cholesterol, and water. This wealth of data has helped redefine our understanding of how GPCRs recognize diverse ligands and transmit signals across the cell membrane, as well as the structural basis for allosteric modulation and biased signaling. The article also discusses the structural diversity within GPCR subfamilies and the comprehensive structural coverage of the opioid subfamily, emphasizing the conserved microswitches and ligand-dependent triggers that control receptor activation. Additionally, it explores the structural framework for GPCR activation, the role of G protein binding and signaling, and the insights into allosteric modulation and oligomerization. Finally, the article highlights the importance of complementary biophysical studies in understanding GPCR conformational dynamics and the potential for using "biased" and allosteric ligands to modulate receptor function.