This chapter summarizes the present knowledge about essential features of the mode of coupling of peptidergic receptors with second messenger systems in the gastrointestinal tissues. It shows that various tissues of the gastrointestinal tract contain diverse families of neuropeptides. Neuropeptides interact with a variety of target cells in the gastrointestinal tract and are involved in the control of multiple physiological functions. Such functions include the regulation of absorptive and secretory processes in epithelial cells, control of the contractile activity of gastrointestinal smooth muscles, modulation of neurotransmission in enteric ganglia and the regulation of gastrointestinal blood flow. The molecular mechanisms of signal transduction activated by opioid receptors have been studied extensively in the tissues of the central nervous system. The second messenger systems coupled to opioid receptors include adenylate cyclase and ion channels. The coupling of neurotensin receptors with second messenger systems has been studied extensively in neuronal cells.