Tachykinins (TKs) are evolutionarily ancient neuropeptides found throughout most bilaterians, characterized by a conserved FX1GX2Ramide carboxy-terminus in protostomes and FXGLMamide in deuterostomes. In mammals, substance P and other TKs have been implicated in health and disease, with important roles in pain, inflammation, cancer, depressive disorder, immune system, gut function, hematopoiesis, sensory processing, and hormone regulation. In invertebrates, the TKs also have multiple functions in the central nervous system and intestine, which have been investigated in detail in the fly Drosophila. This chapter reviews the organization and evolution of TK precursors, peptides, and their receptors in protostomes and deuterostomes. It provides a comparative description of the distribution and functions of TKs in bilaterian organisms. Several TK functions appear to be partly conserved across these animals. Thus, in Drosophila, recent studies indicate roles of TKs in early olfactory and gustatory processing, neuromodulation in circuits controlling locomotion and food search, nociception, aggression, metabolic stress, and hormone release. TK signaling also regulates motility and lipid metabolism in the Drosophila intestine, and during the development TKs play roles in growth, regeneration, and inflammation. In general, TKs are widely distributed and act in neuronal circuits at short range as neuromodulators or co-transmitters. A curiosity is that separate genes encode mimetic TKs in frog skin and in the salivary glands or venom glands of insects. The insect gland TKs are injected into prey animals to cause vasodilation and paralysis, respectively.