Members of the Zic family of zinc finger transcription factors play critical roles in a variety of developmental processes. They are involved in development of neural tissues and the neural crest, in left-right axis patterning, in somite development, and in formation of the cerebellum. In addition to their roles in cell-fate specification, zic genes also promote cell proliferation. Further, they are expressed in postmitotic cells of the cerebellum and in retinal ganglion cells. Efforts to determine the role of individual zic genes within an array of developmental and cellular processes are complicated by overlapping patterns of zic gene expression and strong sequence conservation within this gene family. Nevertheless, substantial progress has been made. This review summarizes our knowledge of the molecular events that govern the activities of zic family members, including emerging relationships between upstream signaling pathways and zic genes. In addition, advancements in our understanding of the molecular events downstream of Zic transcription factors are reviewed. Despite significant progress, however, much remains to be learned regarding the mechanisms through which zic genes exert their function in a variety of different contexts.