The spinal cord has been used as a model to dissect the mechanisms that govern the patterning of tissues during animal development, since the principles that rule the dorso-ventral patterning of the neural tube are applicable to other systems. Signals that determine the dorso-ventral axis of the spinal cord include Sonic hedgehog (Shh), acting as a bona fide morphogenetic signal to determine ventral progenitor identities, and members of the Bmp and the Wnt families, acting in the dorsal neural tube. Although Wnts have been initially recognized as important in proliferation of neural progenitor cells, their role in the dorso-ventral patterning has been controversial. In this review, we discuss recent reports that show an important contribution of the Wnt canonical pathway in dorso-ventral pattern formation. These data allow building a model by which the ventralizing activity of Shh is antagonized by Wnt activity through the expression of Gli3, a potent inhibitor of the Shh pathway. Therefore, antagonistic interactions between canonical Wnt, promoting dorsal identities, and Shh pathways, inducing ventral ones, would define the dorso-ventral patterning of the developing central nervous system. Developmental Dynamics 239:69–76, 2010. © 2009 Wiley-Liss, Inc.