Perhaps the most fundamental aspect of development is the acquisition by a cell of a terminal and stable fate because it marks the usually irreversible commitment to a specific morphology and function. Understanding the molecular mechanisms that control this process has profound implications for stem cell biology and cancer research. Because cell fate commitment is regulated by transcription factors acting as master switches, a mechanistic understanding of the process requires revealing the gene regulatory networks downstream of these factors. We discuss the biological functions of the proneural targetome in the light of signaling pathways, and the recent progress on computational target gene predictions using cisTargetX.