The isolation and purification of somatostatin (SS), exactly 30 years ago, has led to the elucidation of physiologic actions of SS. This cyclic peptide is produced in the hypothalamus, throughout the central nervous system, as well as in most major peripheral organs and inhibits hormone release from the anterior pituitary gland, pancreas and the gastro-intestinal tract. The potent inhibitory actions of SS not only led to the clinical application of this peptide, but also resulted in the development of SS-analogues, among which octreotide and lanreotide are most well known and clinically used for several distinct disorders. Almost ten years ago, five different SS receptor subtypes (sst1-5) were identified. These receptor subtypes are variably expressed in distinct tissues and bind with varying affinity to the different SS-analogues, providing an excellent tool to unravel the (patho-) physiological function of the five sst subtypes. Following an overview upon the latest developments in SS receptor physiology and established diagnostic and therapeutic efficacy of SSanalogues in several challenging neuroendocrine disorders, this review predominantly focuses upon the latest developments of (clinically) potential novel sst subtype specific analogues as well as universal binding SS-peptides. Also, the role of potential SS antagonists is assessed. Furthermore, the most recent insights concerning targeted sst-mediated chemo- or radiotherapy are discussed, which offers new therapeutic and diagnostic opportunities for patients harbouring sst-positive neuroendocrine diseases. Finally, acknowledged side effects and possible pitfalls of the use of SS-analogues are discussed.