This chapter distills landmark trials that shape day-to-day internal medicine rheumatology. In rheumatoid arthritis, TEMPO, TICORA, GO-FORWARD, and AGREE collectively established the modern playbook: treat-to-target with frequent assessment; start effective therapy early; favor combination strategies (biologic + methotrexate) for faster, deeper remission; and protect joints by limiting radiographic progression. In ANCA-associated vasculitis, RAVE and RITUXVAS validated rituximab as an induction option comparable to cyclophosphamide—particularly valuable in relapsing disease and when alkylator toxicity is a concern—while PEXIVAS overturned routine plasma exchange and endorsed reduced-dose glucocorticoids to curb infections without sacrificing survival or kidney outcomes. In systemic lupus erythematosus, the BLISS trials positioned belimumab as the first targeted biologic to improve global disease control and reduce flares with steroid-sparing potential. Health-system stewardship is addressed by NOR-SWITCH, showing that a single switch from originator infliximab to a biosimilar preserves efficacy, safety, and immunogenicity. Finally, CARES reminds clinicians that urate lowering is not just biochemical: despite noninferior MACE, febuxostat carried higher cardiovascular and all-cause mortality than allopurinol, reshaping gout first-line choices. Together these studies underpin guideline recommendations and offer practical, scenario-based insights for everyday inpatient and outpatient care.