Importance of the field: In recent years, scientific work has been intensified to unravel new (patho-) physiological insights, particularly regarding the functional role of somatostatin (SRIF) receptor subtype 5 (sst) and the development of novel sst(5)-targeted SRIF analogues, in order to broaden medical therapeutic opportunities in patients suffering from neuroendocrine diseases. Areas covered in this review: The scope of this review is primarily focused upon recent insights in sst(5)-receptor physiology, novel sst(5)-targeted treatment options predominantly directed towards pituitary adenomas, and gastroenteropancreatic neuroendocrine tumours. What the reader will gain: An understanding of the potential that novel sst(5)-targeted SRIF analogues might have in the medical treatment of Cushing's disease and acromegaly, as demonstrated by translational research, based on pathophysiological data combined with results from clinical trials. Take home message: The role of targeting sst(5) in gastroenteropancreatic neuroendocrine tumours remains to be established. The sst(5) subtype might function as sst(2) modulator in terms of receptor internalization and desensitization, and seems less important compared with sst(2)-preferring SRIF analogues in the regulation of human insulin secretion by the pancreas. Finally, absence of sst(5) in corticotroph adenomas could be related to tumour aggressiveness in Cushing's disease.