Focusing on melatonin secreted from the pineal body of the brain, melatonin receptor agonist Ramelteon (Product name: Rozerem) which was totally different from conventional hypnotics was discovered in Japan. Drug discovery does not come true overnight. Starting with disease and target selection, construction of screening system, drug design, optimization study, toxicity testing, clinical trials and many years of trial and error are repeated tremendously. Only one compound that has been thought out and carefully nurtured by the single-minded many researchers finally reach the goal (product). The burden of the pharmaceutical company is heavy under the limitations of low molecule drug discovery and the exhaustion of drug discovery targets, and unless new strategies to enhance the success rate are taken, the discovery of new medicine can't be hoped at all. In order to continue to maintain world-class drug discovery capabilities and to make drug discovery a reality, aggressive cooperation of industry, government and academia will create highly original results in Japan. I would like to mention how to accomplish the drug discovery through my thorns path leading to drug discovery. I really hope that one grain of drug created by many hard work researchers will present a smile to many patients.