Biosynthetic secretion mobilizes about a third of the human proteome from the Endoplasmic Reticulum (ER) in route to cellular and extracellular destinations. Traffic from the ER to the Golgi Complex begins at distinct sites on the ER, the ER exit sites (ERES), which are functionally and physically connected with the Golgi. ERES are the first sorting sites in the secretory pathway. This chapter explores key molecular functionalities of the ERES.