Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease primarily affecting the synovial joints, leading to progressive disability and premature death. Understanding the pathological mechanisms driving RA progression is crucial for developing effective treatments. This review discusses the etiology and pathology of RA at specific stages: triggering, maturation, targeting, and fulminant stages. Modern pharmacologic therapies, including conventional, biological, and novel small molecule disease-modifying anti-rheumatic drugs (DMARDs), remain the mainstay of treatment. Despite significant progress, many patients do not respond effectively to current therapies, highlighting the need for new drugs. The review also explores recent advances in understanding RA pathogenesis and potential next-generation therapeutics. Key factors in RA pathogenesis include genetic and environmental triggers, such as citrullinated protein antibodies (ACPA), which are associated with aggressive clinical phenotypes. Environmental triggers like smoking, infections, and dietary factors play a role in ACPA production and disease progression. The review highlights the importance of early diagnosis and the continuous monitoring of disease activity to adjust treatment regimens. Conventional synthetic DMARDs, biological DMARDs, and novel small molecule drugs are discussed, along with their mechanisms of action and side effects. The review emphasizes the need for further research to develop personalized medicine and improve patient outcomes.Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease primarily affecting the synovial joints, leading to progressive disability and premature death. Understanding the pathological mechanisms driving RA progression is crucial for developing effective treatments. This review discusses the etiology and pathology of RA at specific stages: triggering, maturation, targeting, and fulminant stages. Modern pharmacologic therapies, including conventional, biological, and novel small molecule disease-modifying anti-rheumatic drugs (DMARDs), remain the mainstay of treatment. Despite significant progress, many patients do not respond effectively to current therapies, highlighting the need for new drugs. The review also explores recent advances in understanding RA pathogenesis and potential next-generation therapeutics. Key factors in RA pathogenesis include genetic and environmental triggers, such as citrullinated protein antibodies (ACPA), which are associated with aggressive clinical phenotypes. Environmental triggers like smoking, infections, and dietary factors play a role in ACPA production and disease progression. The review highlights the importance of early diagnosis and the continuous monitoring of disease activity to adjust treatment regimens. Conventional synthetic DMARDs, biological DMARDs, and novel small molecule drugs are discussed, along with their mechanisms of action and side effects. The review emphasizes the need for further research to develop personalized medicine and improve patient outcomes.