Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and resultant cartilage/bone destruction. In recent years, various kinds of molecular targeted drugs, such as anti-TNF-α monoclonal antibody (mAb), anti-IL-6 receptor mAb, CTLA4-Ig, and JAK inhibitor, have been used in the treatment of RA. Despite differences in the molecular targets of these drugs, they strongly inhibit bone erosion and synovitis even in patients with high disease activity. Recent studies have revealed that these drugs exert direct effects on osteoclasts, although little is known about the differences in mode of action. We have originally established an intravital imaging system for evaluating the in vivo pharmacological actions of drugs in living mice. By means of this system, we revealed that different molecular targeted drugs acted at specific therapeutic points during osteoclastic bone destruction with different efficacies. We found that blockade of TNF-α and IL-6 receptor markedly inhibited the bone resorptive function of mature osteoclasts, whereas CTLA-4 Ig mainly affected the mobility of osteoclast precursors. Furthermore, the JAK inhibitor blocked both the bone resorptive function of mature osteoclasts and the migration of osteoclast precursors to the bone surface during inflammatory bone destruction. These findings enable us to grasp the real modes of action of drugs, optimizing the usage of drug regimens. In this symposium, we show the latest data, and discuss the further application of intravital imaging techniques in the field of immunopharmacology.