This chapter reviews that peptides are essential to many pharmacological processes as they are often of great interest in the drug-discovery process. It is the most challenging goals of modern medicinal chemistry to find rational principles for transforming the information provided by peptide ligands into lowmolecular-weight non-peptide molecules that bind to a target receptor. Such compounds are called peptidomimetics. The chapter discusses that low molecular weight peptidomimetics elicit similar pharmacodynamic effects as the native peptide and are expected to possess desirable pharmacokinetic properties superior to natural peptides, including good oral activity and long duration of action. Such compounds are; therefore, considered more useful targets for the drug discovery process. In principle, two types of peptidomimetics can be depicted. In the first one, the proposed pharmacophoric groups of the native peptide are kept in the correct spatial arrangement, but the peptide backbone is replaced with a non-peptidic scaffold. Such a scaffold may be reduced amides, N-methylated amides, D-aminoacids or any other organic scaffold, not related to a regular peptide bond. The second type does not necessarily hold any of the proposed pharmacophoric elements and may be structurally very distinct from the native peptide. The binding mode of such peptidomimetics is often quite different from the binding mode of the native peptide, but the pharmacological consequence is the same. Today, an extensive pool of peptidomimetic antagonists of G-protein coupled peptide receptors are known, while the number of nonpeptidic agonists is limited to agonists for angiotensin, cholecystokinin, bradykinin, opioid, arginine vasopressin, and somatostatin receptors.