To understand higher brain function, we need to understand the cellular function in a cell-type-specific manner. In recent decades, cell manipulation techniques termed chemogenetics (e.g., DREADD) have enabled cell-type-specific control of nerve activity in vivo. These are powerful for elucidating brain function in live animals. However, artificially-designed receptors evoke unnatural cellular signals in these methods; thus, they may not reflect physiological responses. We have recently focused on "molecular-targeted chemogenetics," which allows the cell-type specific regulation of target endogenous receptors. This review describes our current results toward "molecular-targeted chemogenetics" along with the recent progress in cell manipulation techniques.