Biological agents targeting a specific molecule have extraordinarily fine specificity and powerful functional capabilities. By the introduction of biological therapy, management of rheumatoid arthritis has undergone a revolution and a paradigm shift. In this review, I will summarize the role in the pathogenesis of rheumatoid arthritis of the molecules targeted by biological agents. Providing evidence obtained in clinical trials and investigator-initiated clinical studies in Japan, the effectiveness and safety of biological therapy in rheumatoid arthritis are discussed. Finally, studies aiming at a personalized strategy with biological agents are listed and the future perspectives toward tailor-made medicine in the field of rheumatology are discussed.