Recent advances in GPCR crystallography have significantly expanded structural coverage of the GPCR superfamily, revealing detailed insights into their function and dynamics. Over 14 distinct GPCRs have been crystallized, with 7 identified in 2012 alone. Structures of active-state GPCRs, including the β2-adrenergic receptor-G-protein complex, have been determined, along with insights into ligand-dependent conformational changes. These structures highlight the role of ligands, ions, lipids, and water in GPCR activation and signaling. The adenosine A2a receptor structure illustrates the receptor as an allosteric machine, with dynamic equilibrium between functional states. Structural data is aiding the understanding of GPCR ligand recognition and signal transduction across the cell membrane, as well as the structural basis of allosteric modulation and biased signaling. GPCRs, despite sharing a common seven-transmembrane topology, exhibit significant structural diversity, with over 800 human GPCRs classified into five major families. Structural studies have revealed key differences in extracellular loops, transmembrane helices, and side chains, leading to varied ligand-binding pockets and functional selectivity. The opioid receptor subfamily, with all four subtypes fully characterized, exemplifies structural diversity within GPCRs. The β2-adrenergic receptor and muscarinic acetylcholine receptors have been extensively studied, revealing conformational changes and interactions critical for GPCR activation. Structural insights into GPCR activation include common helical rearrangements and microswitches, such as the D[E]RY motif in helix III, which stabilizes global movements and primes the receptor for G protein binding. Ligand-dependent "triggers" such as Trp6.48 and Tyr7.53 play crucial roles in activating GPCRs, with variations in these residues affecting receptor function and signaling. The β2-adrenergic receptor's activation involves conformational changes in helices V and VI, with movements influenced by ligand binding and G protein interactions. Crystal structures of GPCR-G protein complexes, such as the β2-adrenergic receptor-Gαβγ complex, reveal conformational changes and interactions essential for signaling. Allosteric regulation of GPCRs by endogenous ions, lipids, and synthetic modulators is also being explored, highlighting their complex allosteric nature. Structural studies have provided new insights into the role of sodium, cholesterol, and other molecules in GPCR function. Molecular modeling and biophysical techniques, including NMR and HDX-MS, are being used to study GPCR dynamics and conformational changes. These approaches are complementing structural data, providing a more comprehensive understanding of GPCR function and dynamics. Future research aims to determine structures of additional GPCR subfamilies, explore the structural basis of G protein and β-arrestin selectivity,Recent advances in GPCR crystallography have significantly expanded structural coverage of the GPCR superfamily, revealing detailed insights into their function and dynamics. Over 14 distinct GPCRs have been crystallized, with 7 identified in 2012 alone. Structures of active-state GPCRs, including the β2-adrenergic receptor-G-protein complex, have been determined, along with insights into ligand-dependent conformational changes. These structures highlight the role of ligands, ions, lipids, and water in GPCR activation and signaling. The adenosine A2a receptor structure illustrates the receptor as an allosteric machine, with dynamic equilibrium between functional states. Structural data is aiding the understanding of GPCR ligand recognition and signal transduction across the cell membrane, as well as the structural basis of allosteric modulation and biased signaling. GPCRs, despite sharing a common seven-transmembrane topology, exhibit significant structural diversity, with over 800 human GPCRs classified into five major families. Structural studies have revealed key differences in extracellular loops, transmembrane helices, and side chains, leading to varied ligand-binding pockets and functional selectivity. The opioid receptor subfamily, with all four subtypes fully characterized, exemplifies structural diversity within GPCRs. The β2-adrenergic receptor and muscarinic acetylcholine receptors have been extensively studied, revealing conformational changes and interactions critical for GPCR activation. Structural insights into GPCR activation include common helical rearrangements and microswitches, such as the D[E]RY motif in helix III, which stabilizes global movements and primes the receptor for G protein binding. Ligand-dependent "triggers" such as Trp6.48 and Tyr7.53 play crucial roles in activating GPCRs, with variations in these residues affecting receptor function and signaling. The β2-adrenergic receptor's activation involves conformational changes in helices V and VI, with movements influenced by ligand binding and G protein interactions. Crystal structures of GPCR-G protein complexes, such as the β2-adrenergic receptor-Gαβγ complex, reveal conformational changes and interactions essential for signaling. Allosteric regulation of GPCRs by endogenous ions, lipids, and synthetic modulators is also being explored, highlighting their complex allosteric nature. Structural studies have provided new insights into the role of sodium, cholesterol, and other molecules in GPCR function. Molecular modeling and biophysical techniques, including NMR and HDX-MS, are being used to study GPCR dynamics and conformational changes. These approaches are complementing structural data, providing a more comprehensive understanding of GPCR function and dynamics. Future research aims to determine structures of additional GPCR subfamilies, explore the structural basis of G protein and β-arrestin selectivity,