β‐Arrestin 1‐GFP or β‐arrestin 2‐GFP were coexpressed transiently with G protein‐coupled receptor kinase 2 within cells stably expressing the orexin‐1, apelin or melanin‐concentrating hormone (MCH), receptors. In response to agonist ligands both the orexin‐1 and apelin receptors were able to rapidly translocate both β‐arrestin 1‐GFP and β‐arrestin 2‐GFP from cytoplasm to the plasma membrane. For the MCH receptor this was only observed for β‐arrestin 2‐GFP. β‐Arrestin 1‐GFP translocated by the apelin receptor remained at the plasma membrane during prolonged exposure to ligand even though the receptor became internalized. By contrast, for the orexin‐1 receptor, internalization of β‐arrestin 1‐GFP within punctate vesicles could be observed for over 60 min in the continued presence of agonist. Co‐internalization of the orexin‐1 receptor was observed by monitoring the binding and trafficking of TAMRA‐(5‐ and 6‐carboxytetramethylrhodamine) labelled orexin‐A. Subsequent addition of an orexin‐1 receptor antagonist resulted in cessation of incorporation of β‐arrestin 1‐GFP into vesicles at the plasma membrane and a gradual clearance of β‐arrestin 1‐GFP from intracellular vesicles. For the melanin‐concentrating hormone receptor the bulk of translocated β‐arrestin 2‐GFP was maintained at concentrated foci close to, or at, the plasma membrane. These results demonstrate very distinct features of β‐arrestin–GFP interactions and trafficking for three G protein‐coupled receptors for which the natural ligands have only recently been identified and which were thus previously considered as orphan receptors.