Three neurotensin (NT) receptors have been cloned to date, two of which, NTS1 and NTS2, belong to the family of seven transmembrane domain receptors coupled to G proteins (GPCRs). NTS1 and NTS2 may activate multiple signal transduction pathways, involving several G proteins. However, whereas NT acts as an agonist towards all NTS1-mediated pathways, this peptide may exert either agonist or antagonist activities, depending on the NTS2-mediated pathway in question. Studies on these receptors reinforce the concept of independence between multiple signals potentially mediated through a single GPCR, generating a wide diversity of functional responses depending on the host cell and the ligand.