This chapter summarizes the significant contribution that research on zebrafish has made toward identifying components of the nodal signaling pathway and defining the functions of nodal proteins during development. Nodal signals are essential for establishing the body plan of vertebrate embryos. Nodal proteins are secreted signaling factors in the transforming growth factor β (TGF β) family that have been found in every vertebrate. In zebrafish, two Nodal-related proteins, Cyclops (Cyc) and Squint (Sqt), have been characterized. Cyc and Sqt are synthesized as proproteins, which are cleaved to make the mature form. The chapter reveals that the cyc and sqt genes have distinct, dynamic expression patterns in the embryo. These expression patterns reflect the complex roles of nodal signals during development and are important for understanding when and where patterning is taking place. In zebrafish and other vertebrates nodal proteins are involved in multiple patterning events during development, including initial specification of the endoderm and mesoderm, formation of the ventral neural tube, and regulation of left–right asymmetry.