Rheumatoid arthritis (RA) is an autoimmune disorder distinguished by synovial inflammation followed by destruction of joint. The pathogenesis of arthritis involves immune imbalance of the endogenous system. Causative factors include immune imbalance, oxidative stress, genetics, and environment. Continued effort has been made to treat RA via chemical, enzymatic, genetic, and hormonal approaches. RA has been reported more in the aged and in women. Arthritis necessitates lifelong administration of drugs to maintain quality of life. The major challenges of treatment are the side effects associated with these drugs. Novel approaches and targets have been explored as alternative measures to relieve pain in RA sufferers. Customary treatment strategies have limited therapeutic capability with episodes of associated side effects. Thus, revolutionary advances in novel RA-targeted drug delivery strategies are needed for efficient therapies and to meet the demand for treatment. The current review summarizes the pathogenesis of RA, its causative factors, and therapeutic approaches. These approaches are discussed with regard to mode of action, pharmacokinetics, marketed products, side effects of individual RA drugs, recent developments, modifications in the delivery of various drugs through targeted ligands, novel drug carriers as vesicular, particulate, self assembled, cellular, ceramic systems, and future prospects.