Decades of accumulated knowledge and improved comprehension of various perspectives on rheumatoid arthritis (RA) pathophysiology has led to the development of new biologic agents that inhibit a specific component of the RA inflammatory process. Especially during the last two decades, several epochal agents which target tumor necrosis factor-alpha, interleukin-1, interleukin-6, CD20-expressing B cell, and cytotoxic T lymphocyte antigen-4 were used in the management of RA and other autoimmune diseases with highly comparable efficacy and safety. Moreover, dozens of innovative agents queue up for clinical trials day by day. Herein, we review the current scenario of RA management in terms of pathogenesis and targeted molecular pathways, and some important controversies in this field as well. Based on the complications that these kinds of diseases pose, it is highly reasonable to hope that further improved therapies and more tailored drugs for RA will be introduced in the near future.