Embryonic development is orchestrated by the activity of signal transduction pathways, amongst which are those downstream of the transforming growth factor β (TGF-β) family. Here I focus on signalling by one of these ligands, NODAL, which is essential for early embryonic axis patterning. I review recent advances in our understanding of how NODAL signalling is transduced from the plasma membrane to the nucleus to regulate the transcription of target genes, and how domains of NODAL activity are established and refined during embryonic development. The duration of signalling is emerging as a key determinant of the specificity of downstream responses in terms of cell fate decisions and I will discuss what is currently known about the underlying mechanisms.