The retrograde trafficking from endosomes to the trans-Golgi network (TGN) is one of the major endocytic pathways to divert proteins and lipids away from lysosomal degradation. Retrograde transported cargos enter the TGN via two itineraries from either the early endosome/recycling endosome or the late endosome and involve various machinery components such as retromer, sorting nexins, clathrin, small GTPases, tethering factors and SNAREs. Recently, the pathway has been recognized for its role in signal transduction, physiology and pathogenesis of human diseases.