The neuropeptide somatostatin is a cyclic tetradecapeptide, which is widely distributed in the peripheral and central nervous system. It mediates a plethora of physiological actions and functions as a neurotransmitter, neuromodulator or trophic factor. Somatostatin activates six receptor subtypes that are expressed differentially in different tissues and are coupled to diverse signalling pathways. In order to elucidate the functional role of the individual receptor subtypes, many investigations focused on the assignment of each receptor to a particular signalling pathway. Signalling pathways involving enzyme (adenylate cyclase, phospholipases, phosphatases) and ion channel systems in native and recombinant receptor systems have been extensively studied. A one to one situation (receptor/pathway) has yet to be established, thus justifying the diverse actions of somatostatin. Recently, a NO/cGMP pathway has been shown to mediate the functions of somatostatin and its receptors. This review will present the findings that support the emerging role of NO/cGMP as a novel signal in SRIF's actions in retinal physiology and somatotroph release.