During the last decade, multi-photon fluorescent microscopy has launched a new trend in the field of biology. By using this advanced imaging technique we have established a new system for visualizing in situ behavior of a diversity of living cells within intact tissues and organs. Among them, we succeeded in visualizing the various dynamic phenomena within bones, a mysterious organ where various kinds of hematopoietic and immune cells are produced and functioning although poorly analyzed by conventional methodology such as histological analyses with decalcified bones. Especially we have focused on the behavior of osteoclast, a kind of specialized macrophage contributing to physiological bone remodeling as well as to bone destruction in arthritis and osteoporosis, and have been revealing novel mechanisms controlling migration and function of osteoclasts in situ. Osteoclasts in vivo have turned out to continuously undergo transition between two functional status, static ‘resorbing’ and moving ‘non-resorbing’ conditions. A novel fluorescent probe detecting local proton secretion has revealed the real mode of bone resorption of osteoclasts in vivo, who seem to recognize specific bone areas to be resorbed. Further analyses detected the mode of functional interaction between osteoclasts and osteoblasts, which was dynamically altered by PTH. This novel bone imaging methodology is sure to, collaborating with conventional histomorphometical analyses, contribute to opening a new era in the field of bone and mineral researches in future.