G protein-coupled receptors (GPCRs) have continued to attract biomedical attention due to their enormous physiological importance and their potential to be targeted with drugs. GPCRs, being the largest family of membrane receptors, transduce very diverse extracellular signaling molecules such as hormones, neurotransmitters, and sensory stimuli. While canonical signaling via G proteins and β-arrestins has been studied in detail, new areas for investigation in the future include emerging complexities in receptor dynamics, biased signaling, and tissue-specific modulation. Productive avenues for progressing GPCR research, therefore, will likely involve correlating high-resolution structural biology with computational approaches that allow for characterizing receptor conformers and the ligand-binding landscape. With the ongoing revolution in cryo-electron microscopy and AI-based simulations, transient states of critical importance for drug design can be observed. On the other hand, diversification of allosteric modulators and biased agonists contributes to system- and subtype-selective targeting of GPCRs with reduced side effects. Functional genomics and single-cell transcriptomics may reveal novel GPCRs as well as context-specific patterns of expression, and they can inform tailored therapeutic approaches. Furthermore, using nanotechnology-based delivery systems and biosensors for possible improvement in drug delivery to GPCRs and monitoring receptor function in vivo, respectively. Joint efforts from pharmacology, structural biology, and systems biology, among others, will be required to unravel receptor cross talk, heteromerization, and intracellular trafficking. The regulatory systems will have to be adapted to novel GPCR-targeted modalities, such as gene editing, synthetic biology, and others. Ultimately, the convergence of multidisciplinary innovation will transform GPCR drug discovery, delivering next-generation therapeutics for challenging diseases of complex biology, including cancer, neurodegeneration, and metabolic disorders. This section delineates strategic lines that will be pursued in the future of GPCR research in terms of the impact on translational research, technology platforms, and precision pharmacology.