In this chapter it is described how, starting from different approaches and through extensive medicinal chemistry studies, several discovery compounds were optimized and reached the development stage. The first tachykinin receptor antagonist to reach the market in 2003 for chemotherapy-induced emesis has been aprepitant. Other clinical candidates (for central nervous system disorders: osanetant, talnetant and saredutant; for irritable bowel syndrome: nepadutant and saredutant) are in advanced clinical phase. The clinical studies reported in the literature and the destiny of the clinical candidates, where available, will be reviewed.