There are five major signaling pathways that control embryogenesis, comprising the Hedgehog, Wnt, TGFβ/Bmp, Notch, and fibroblast growth factor (FGF) signaling families. Together these control cell proliferation, cell survival, changes in cell shape, migration, adhesion, and cell differentiation. Mutation in components of these pathways results in a number of human syndromes. This chapter discusses the five key signaling pathways that control embryonic development. It describes the various roles, mechanisms of action of each pathway and highlights syndromes that are due to mutations in components of these signaling pathways. The chapter explains how mutations in transcription factors, matrix molecules, and epigenetic factors can affect embryonic development. During embryonic development, the vertebrae and axial musculature develop from somites, which are epithelial balls that periodically bud off from the unsegmented paraxial mesoderm. Deregulation of the notch pathway affects somite development by deregulating the clock and preventing the formation of boundaries.