The secretory pathway ensures the proper delivery of secreted proteins to the extracellular medium and of transmembrane proteins to almost all membrane cellular compartments. During their transport in the different compartments making up this pathway, newly synthesized proteins are modified and dispatched to their final destinations. So far, this pathway has mostly been studied in tissue cultured cells or yeast but recently, mutations in genes encoding key proteins of this pathway have been shown to lead to severe developmental defects in different model organisms. In this review, we describe how specific steps of epithelial, cartilage, notochord and brain development as well as body axis formation are controlled by the early secretory machinery illustrating that it is as crucial as transcriptional programs.