The original hedgehog (hh) gene was found in Drosophila and named for the appearance of a mutant phenotype which causes an embryo to be covered with pointy denticles, thus resembling a hedgehog. The hedgehog family consists of sonic hedgehog (Shh), desert hedgehog (Dhh), and Indian hedgehog (Ihh). Shh is found in vertebrates and the best studied ligand of the hedgehog signaling pathway (Gilbert, 2000). It plays an important role in regulating vertebrate organogenesis, such as in the growth of digits on limbs and organization of the brain, and earlier studies also show that it is important during retinal development (for a review, see Amato et al., 2004). Hedgehog expression drives waves of neurogenesis in animal retina, although genetic programs that control its expression are poorly elucidated. Recently, a novel transcriptional cascade which involves the atonal and Iroquois gene family was proposed in the regulation of hedgehog waves during vertebrate retinal development (Choy et al., 2010). This chapter will focus on Shh by addressing its signaling mechanisms and roles in vertebrate eye development, as well as a novel finding in retinogenesis.