Somatostatin (SST) is a widely distributed peptide occurring in two forms SST-14 (with 14 amino acids) and SST-28 (with 28 amino acids). SST has multiple functions including modulation of secretion of growth hormone, insulin, glucagon, and gastric acid, in addition to having potent anti-proliferative effects. The actions of somatostatin are mediated via five high affinity membrane associated receptors (SSTR1-5), and studies utilizing subtype selective peptides have provided evidence that somatostatin subtype 2 receptors (SSTR2) regulate secretion of growth hormone and glucagon which suggests a role for SSTR2 in the treatment of diabetes and diabetes-related pathologies, including retinopathy, neuropathy and nephropathy. In addition, somatostatin and SSTR2 have been implicated in a variety of other biological processes such as nociception, inflammation and cell proliferation. Recent results from our laboratory in which potent, selective SSTR2 agonists have been identified and optimized using an iterative analogue library approach will be presented. Highlights include the extensive use of controlled, sequential cross-coupling reactions of polyhalogenated quinolines in library synthesis.