Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease that primarily affects the synovial joints, but RA-associated systemic inflammation can cause various extra-articular manifestations and comorbidities. Despite a remarkable therapeutic revolution in recent years, rheumatologists are confronted by many difficulties in the daily practice of managing RA patients. This Special Issue includes six reviews and seven original articles that provide up-to-date information on the concepts of RA pathogenesis and advances in diagnosis and treatment strategies using biological and nonbiological disease-modifying antirheumatic drugs (DMARDs). The clinical significance of autoantibodies as biomarkers and long-term outcomes of joint damage and function in RA patients are also addressed. Additionally, this collection highlights the management of RA patients with extra-articular manifestations and comorbidities such as interstitial lung disease, chronic kidney disease, osteoporosis, and malignancy. This Special Issue will contribute to optimizing the use of the existing DMARDs and managing individual RA patients in a more personalized manner.