After its discovery in 1931, substance P (SP) remained the only mammalian member of the family of tachykinin peptides for several decades. Tachykinins thus refer to peptides sharing the common C-terminal amino acid sequence Phe-X-Gly-Leu-Met x NH2. In recent years the family of mammalian tachykinins has grown with the isolation of two novel peptides from bovine and porcine central nervous system (CNS), neurokinin A and neurokinin B. In parallel with the identification of multiple endogenous tachykinins several classes of tachykinin receptors were discovered. The receptors described so far are named tachykinin NK1 receptor, tachykinin NK2 receptor and tachykinin NK1 receptor, respectively. The present review focuses on the pharmacology and putative function of tachykinin NK1 receptors in brain. The natural ligand with the highest affinity for the tachykinin NK1 receptor is SP itself. The C-terminal sequence is essential for activity, the minimum length of a fragment with reasonable affinity for the tachykinin NK1 receptor is the C-terminal hexapeptide. A rapid advance of knowledge was caused by development of non-peptidic tachykinin NK1 receptor antagonists. This area is under rapid development and a variety of different chemical classes of compounds are involved. Species-dependent affinities of tachykinin NK1 receptor antagonists reveal two clusters of compounds, targeting the tachykinin NK1 receptor subtype found in guinea pig, human or ferret or the one in rat or mouse, respectively. The most recently developed compounds are highly selective, enter the brain and are orally bioavailable. Distinct behavioural effects in experimental animals suggest the involvement of tachykinin NK1 receptors in nociceptive transmission, basal ganglia function or anxiety and depression. Recent clinical trials in man showed that tachykinin NK1 receptor antagonists are effective in treating depression and chemotherapy-induced emesis. Therefore, it is well possible that tachykinin NK1 receptor antagonists will be clinically used for treatment of specific CNS disorders within a short period of time.