runt-related (RUNX) genes encode evolutionarily conserved transcription factors that play essential roles during development and adult tissue homeostasis. RUNX proteins regulate the transition from proliferation to differentiation in a variety of cell lineages. Moreover, they control the diversification of distinct cellular phenotypes in numerous tissues. Alterations of RUNX functions are associated with several cancers and other human pathologies, underscoring the vital roles of these transcription factors in adult organs. Insights into the functions and regulations of mammalian RUNX proteins have been provided mostly by studies of RUNX involvement in mechanisms of hematopoietic and skeletal development and disease. A growing number of recent investigations are revealing new functions for RUNX family members during the development of the mammalian nervous system. This review will discuss recent progress in the study of RUNX protein involvement in mammalian neural development, with emphasis on the differentiation of olfactory, sensory, and motor neuron lineages. J. Cell. Biochem. 107: 1063–1072, 2009. © 2009 Wiley-Liss, Inc.