Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation which ultimately leads to severe disability and premature mortality. It has a global prevalence of around 1% with the incidence among women being 2–3 times more than in men. The pathogenesis of the disease involves preclinical RA, genetic factors, and environmental factors. The RA has no known cure and the primary aim of treatment remains to attain lowest possible disease activity and recovery if possible. The present review highlights the literature on the different treatment options available for the treatment of RA, their mechanisms of action, side effects, and novel drug delivery systems that are in use for drug administration with the main focus on novel drug delivery systems of non-steroidal anti-inflammatory drugs. Different classes of drugs such as corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying anti-rheumatic drugs (DMARDs), and biologics are discussed with examples of most widely used drugs among each class. Conventional drug therapy has many disadvantages like low solubility and permeability, poor bioavailability, degradation by gastrointestinal enzymes, first pass metabolism, food interactions, and toxicity. Novel drug delivery systems like microspheres, nanoparticles, dendrimers, liposomes, and so on are promising tools as they have been successful in overcoming the disadvantages associated with conventional drug delivery system. The present review squares the various novel drug delivery systems that have been explored for administering anti-rheumatic drugs and the advantages associated with these novel drug delivery systems in comparison to conventional drug delivery systems.