The prevailing approach within the field of craniofacial development is focused on finding a balance between tissues (e.g., facial epithelia, neuroectoderm, and neural crest) and molecules (e.g., bone morphogenetic proteins, fibroblast growth factors, Wnts) that play a role in sculpting the face. We are rapidly learning that neither these tissues nor molecular signals are able to act in isolation; in fact, molecular cues are constantly reciprocating signals between the epithelia and the neural crest in order to pattern and mold facial structures. More recently, it has been proposed that this crosstalk is often mediated and organized by discrete organizing centers within the tissues that are able to act as a self-contained unit of developmental potential (e.g., the rhombomere and perhaps the ectomere). Whatever the molecules are and however they are interpreted by these tissues, it appears that there is a remarkably conserved mechanism for setting up the initial organization of the facial prominences between species. Regardless of species, all vertebrates appear to have the same basic bauplan. However, sometime during mid-gestation, the vertebrate face begins to exhibit species-specific variations, in large part due to differences in the rates of growth and differentiation of cells comprising the facial prominences. How do these differences arise? Are they due to late changes in molecular signaling within the facial prominences themselves? Or are these late changes a reflection of earlier, more subtle alterations in boundaries and fields that are established at the earliest stages of head formation? We do not have clear answers to these questions yet, but in this chapter we present new studies that shed light on this age-old question. This chapter aims to present the known signals, both on a molecular and cellular level, responsible for craniofacial development while bringing to light the events that may serve to create difference in facial morphology seen from species to species.