The somatostatin receptor subtypes 1-5 (sst(1)-sst(5)) exhibit different intracellular trafficking and endosomal sorting after agonist exposure. The internalization of the somatostatin receptor subtypes sst(2), sst(3) and sst(5) occurs to a much higher extent after somatostatin exposure than of sst(1) or sst(4). After endocytosis, sst(2) and sst(5) recycle to the plasma membrane, whereas sst(3) is predominantly down-regulated. This review will focus on the molecular mechanisms of the differential intracellular trafficking of sst(2), sst(3) and sst(5), and discusses our current knowledge on somatostatin receptor interacting proteins.