Recent progress in chemical biology research has accelerated the target protein identification of biologically active small molecules, including naturally occurring ligands. It is widely recognized that a biologically active natural product functions as a "key" that fits a specific protein "lock." However, recent studies have revealed multiligandable nature of natural products that works as "multiple keys" (or a "master key") fitting multiple "locks" in a biological event. Biological experiments using natural products as ligands have often provided puzzling results, which can likely be attributed to their multiligandability. Thus, a novel research direction dealing with multiliganbale natural product ligand based on their target identification is strongly desired. This review focuses on the current status of natural products chemistry based on their target identification, and suggest the future direction, named chemical biological chemistry (Chem-Bio-Chem).