Background: The development of RA is influenced by an intricate combination of genetic, environmental, and immunological variables, resulting in persistent inflammation and damage to the joints. The development of the illness is influenced by genetic predisposition, namely involving HLA-DRB1 and other susceptibility genes, as well as environmental triggers including smoking and infections. Rheumatoid arthritis (RA) is characterized by chronic inflammation, which is caused by the activation of both innate and adaptive immune cells in an uncontrolled manner. The inflammatory response and joint degradation are mediated by important cytokines such as TNF-α, IL-1, and IL-6, as well as intracellular signaling pathways including NF-κB, JAK-STAT, and MAPK. Effector cells, such as synovial fibroblasts, osteoclasts, and chondrocytes, have significant involvement in the degenerative processes of rheumatoid arthritis (RA). Comprehending these pathways has resulted in the creation of focused treatments that have greatly improved the control of RA. This thorough review examines the development of pharmacologic treatments for rheumatoid arthritis, focusing on the shift from conventional disease-modifying antirheumatic drugs (DMARDs) to biologic medications and the rise of Janus kinase (JAK) inhibitors. Materials and method:A systematic review was conducted during June 2021 to July 2022 using the MeSH Terms rheumatoid arthritis, inflammatory disorders, immunologic bone disorders. Pubmed, Scopus, Embase and google scholar databases were also searched with the same search strategy and the references of selected journals were scanned to try to find more studies. Conclusion: The pathogenesis of RA involves a complex interplay of genetic, environmental, and immunological factors that lead to chronic inflammation and joint destruction. Genetic predisposition, particularly involving HLA-DRB1 and other susceptibility genes, and environmental triggers such as smoking and infections, set the stage for the disease. The dysregulated immune response, characterized by the activation of innate and adaptive immune cells, drives the chronic inflammation seen in RA. Key cytokines such as TNF-α, IL-1, and IL-6, along with intracellular signaling pathways like NF-κB, JAK-STAT, and MAPK, mediate the inflammatory response and joint destruction. Effector cells, including synovial fibroblasts, osteoclasts, and chondrocytes, play crucial roles in the pathological mechanisms of RA. Understanding these mechanisms has led to the development of targeted therapies that have significantly improved the management of RA.This comprehensive overview covers the evolution of pharmacologic therapies for rheumatoid arthritis, highlighting the transition from traditional DMARDs to biologic agents and the emergence of JAK inhibitors.