The formation of functional neural circuits in the vertebrate central nervous system (CNS) requires that appropriate numbers of the correct types of neuronal and glial cells are generated in their proper places and times during development. In the embryonic CNS, multipotent progenitor cells first acquire regional identities, and then undergo precisely choreographed temporal identity transitions (i.e. time-dependent changes in their identity) that determine how many neuronal and glial cells of each type they will generate. Transcription factors of the basic-helix-loop-helix (bHLH) family have emerged as key determinants of neural cell fate specification and differentiation, ensuring that appropriate numbers of specific neuronal and glial cell types are produced. Recent studies have further revealed that the functions of these bHLH factors are strictly regulated. Given their essential developmental roles, it is not surprising that bHLH mutations and de-regulated expression are associated with various neurological diseases and cancers. Moreover, the powerful ability of bHLH factors to direct neuronal and glial cell fate specification and differentiation has been exploited in the relatively new field of cellular reprogramming, in which pluripotent stem cells or somatic stem cells are converted to neural lineages, often with a transcription factor-based lineage conversion strategy that includes one or more of the bHLH genes. These concepts are reviewed herein.