Cell surface antigens, cytokines, receptors, and signal transduction molecules that are centrally involved in the pathogenesis of rheumatic diseases have been elucidated, and therapeutic targets have been identified. Molecular-targeted drugs are now available, which can treat rheumatoid arthritis and other diseases, including psoriatic arthritis, ankylosing spondylitis, and juvenile idiopathic arthritis. These targeted drugs have been rapidly developed and have shown potential for achieving clinical remission in many rheumatic diseases. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) play major roles in rheumatoid arthritis, and IL-17 and IL-23 play crucial roles in spondyloarthritis. Biological disease-modifying anti-rheumatic drugs (bDMARDs) that specifically inhibit the actions of these cytokines and targeted synthetic DMARDs (tsDMARDs) such as Janus Kinase (JAK) inhibitors have been approved, increasing the treatment options. Molecular-targeted drugs also hold promise for treating collagen diseases, including systemic lupus erythematosus, systemic sclerosis, and vasculitis. However, some drawbacks related to their use persist, including high drug costs and the risk of adverse events such as infectious diseases. Therefore, the criteria for selecting patients who are most likely to benefit from these drugs should be developed.