G protein-coupled receptors (GPCRs) are the most studied drug targets due to their involvement in human pathophysiology and pharmacological tractability. A comprehensive analysis of all GPCR drugs and agents in clinical trials reveals that 481 drugs (34% of FDA-approved drugs) act on 107 unique GPCR targets. Approximately 320 agents are in clinical trials, with 36% targeting 64 novel GPCR targets without approved drugs. The number of biological drugs, allosteric modulators, and biased agonists has increased. Major disease indications for GPCR modulators show a shift towards diabetes, obesity, and Alzheimer's disease, while other central nervous system disorders remain highly represented. The 227 non-olfactory GPCRs yet to be explored in clinical trials have significant therapeutic potential, particularly in genetic and immune system disorders. An interactive online resource is provided for analyzing GPCR drug discovery trends. The majority of drug targets are in five protein families: GPCRs, ion channels, kinases, nuclear hormone receptors, and proteases. GPCRs account for about 27% of the global market share of therapeutic drugs. GPCRs form the largest human membrane protein family, with approximately 800 members, of which about half are olfactory receptors. The superfamily is divided into classes and families based on evolutionary homology and common physiological ligands. Recent advances in receptor pharmacology, structural biology, and biotechnology have opened new avenues for GPCR drug discovery. Allosteric modulation can alter receptor structure, dynamics, and function to achieve therapeutic advantages. Biased agonism, which preferentially activates desired intracellular signaling pathways, has expanded our understanding of receptor activation. Structure-based drug discovery has advanced with the crystal structures of 43 unique receptors and 196 ligand complexes. Peptide/protein receptors are potential targets for biological drugs, with 130 (33%) being peptide or protein receptors. Many more receptors have become accessible through techniques that exploit natural protein-protein interactions or develop specific antibodies and derivatives. Orphan GPCRs, which have yet to have their endogenous ligands discovered, are also being explored for new therapeutic applications. Biologics such as monoclonal antibodies are well-established therapeutic modalities, accounting for 27-33% of new FDA-approved drugs. Allosteric modulators offer an attractive novel mechanism for drug development. The success rates of GPCR-targeted agents in clinical trials are higher than the average for all investigated agents. The proportion of GPCR-targeted biologics is higher in early-stage clinical trials. The focus on target selectivity rather than polypharmacology is increasing, with earlier trials showing higher selectivity. The indications for GPCR-targeted agents are expanding into new areas such as Alzheimer's disease and obesity. Central nervous system disorders remain highly represented among GG protein-coupled receptors (GPCRs) are the most studied drug targets due to their involvement in human pathophysiology and pharmacological tractability. A comprehensive analysis of all GPCR drugs and agents in clinical trials reveals that 481 drugs (34% of FDA-approved drugs) act on 107 unique GPCR targets. Approximately 320 agents are in clinical trials, with 36% targeting 64 novel GPCR targets without approved drugs. The number of biological drugs, allosteric modulators, and biased agonists has increased. Major disease indications for GPCR modulators show a shift towards diabetes, obesity, and Alzheimer's disease, while other central nervous system disorders remain highly represented. The 227 non-olfactory GPCRs yet to be explored in clinical trials have significant therapeutic potential, particularly in genetic and immune system disorders. An interactive online resource is provided for analyzing GPCR drug discovery trends. The majority of drug targets are in five protein families: GPCRs, ion channels, kinases, nuclear hormone receptors, and proteases. GPCRs account for about 27% of the global market share of therapeutic drugs. GPCRs form the largest human membrane protein family, with approximately 800 members, of which about half are olfactory receptors. The superfamily is divided into classes and families based on evolutionary homology and common physiological ligands. Recent advances in receptor pharmacology, structural biology, and biotechnology have opened new avenues for GPCR drug discovery. Allosteric modulation can alter receptor structure, dynamics, and function to achieve therapeutic advantages. Biased agonism, which preferentially activates desired intracellular signaling pathways, has expanded our understanding of receptor activation. Structure-based drug discovery has advanced with the crystal structures of 43 unique receptors and 196 ligand complexes. Peptide/protein receptors are potential targets for biological drugs, with 130 (33%) being peptide or protein receptors. Many more receptors have become accessible through techniques that exploit natural protein-protein interactions or develop specific antibodies and derivatives. Orphan GPCRs, which have yet to have their endogenous ligands discovered, are also being explored for new therapeutic applications. Biologics such as monoclonal antibodies are well-established therapeutic modalities, accounting for 27-33% of new FDA-approved drugs. Allosteric modulators offer an attractive novel mechanism for drug development. The success rates of GPCR-targeted agents in clinical trials are higher than the average for all investigated agents. The proportion of GPCR-targeted biologics is higher in early-stage clinical trials. The focus on target selectivity rather than polypharmacology is increasing, with earlier trials showing higher selectivity. The indications for GPCR-targeted agents are expanding into new areas such as Alzheimer's disease and obesity. Central nervous system disorders remain highly represented among G