It is well-known that Japan was the third country, after the United States and the United Kingdom, to become self-sufficient in penicillin manufacture, as early as 1948. Besides the production of penicillin, much effort was made nationwide in exploratory research on anti-infective, anti-cancer, and agricultural antibiotics, and also other bioactive microbial products. One can list upwards of 117 useful antibiotics and related agents of Japanese origin, and among them, 41 agents have been licensed out around the world. The first antibiotic from Japan was colistin (discovered in 1950) followed by well-known agents such as mitomycin C (1955), kanamycin (1957), bleomycin (1965), cefazolin (1969), amikacin (1972), piperacillin (1976), norfloxacin (1977), cefoperazone (1978), ofloxacin (1980), clarithromycin (1984), meropenem (1987), and others. The major group is the beta-lactam antibiotics (up to 15), followed by 7 fluoroquinolones and anti-cancer and agricultural antibiotics (4 of each). Noteworthy was the expansion of antibiotics research into bioactive microbial products, which led to the discovery of extremely beneficial agents for human quality of life (QOL), such as pravastatin for hyperlipidemia and tacrolimus for atopic diseases. It is to be expected that Japan will continue a high level of activity in exploratory research on beneficial chemotherapeutic agents in the twenty-first century. The Japanese Society of Chemotherapy (JSC), established in 1953, has played a central role for about a half century in the evaluation of novel agents discovered in Japan and those introduced from abroad. Besides the evaluation of chemotherapeutic agents, both fundamentally and clinically, the JSC has taken an active part in the establishment of a variety of guidelines for chemotherapy and in the education of clinical scientists who have evaluated all agents of Japanese origin appropriately.