Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease affecting an estimated 0.5–1% of people worldwide that, left untreated, can cause substantial and often irreversible joint damage. Current evidence suggests RA begins years before any joint symptoms appear, with immune dysregulation first taking hold at mucosal surfaces such as the lung, gut, and periodontium, where genetic susceptibility, microbial dysbiosis, and protein citrullination combine to erode immunological tolerance. Recent work has clarified how the gut–joint axis, cytokine networks, synovial fibroblast and macrophage heterogeneity, and anti-citrullinated protein antibodies (ACPA) each contribute to disease pathophysiology. This review then turns to the therapeutic landscape, which continues to evolve quickly. We cover treat-to-target strategies, conventional and biologic disease-modifying antirheumatic drugs (DMARDs), the growing role of biosimilars, the recalibrated safety profile of Janus kinase (JAK) inhibitors following the ORAL Surveillance trial and the 2025 EULAR recommendations, and newer cellular and nanomedicine approaches, including CD19-directed chimeric antigen receptor (CAR) T-cell therapy and CAR-regulatory T-cell therapy. We close by outlining the field’s unmet needs, particularly around precision medicine, better management of difficult-to-treat RA, and prevention in high-risk individuals.