Overexpression of exogenous lineage-specific transcription factors could directly induce terminally differentiated somatic cells into target cell types. However, the low conversion efficiency and the concern about introducing exogenous genes limit the clinical application. With the rapid progress in genome editing, the application of CRISPR/dCas9 has been expanding rapidly, including converting somatic cells into other types of cells in vivo and in vitro. Using the CRISPR/dCas9 system, direct neuronal reprogramming could be achieved by activating endogenous genes. Here, we will discuss the latest progress, new insights, and future challenges of the application of the dCas9 system in direct neuronal reprogramming.