A key issue in development is how to specify single isolated precursor cells to adopt a distinct fate from a group of naive cells. Studies on the development of Drosophila external sensory (ES) organs have revealed multiple mechanisms to specify single sensory organ precursors (SOPs) from clusters of cells with equivalent neural potential. Initially single SOPs are selected in part through cell-cell competition from clusters of ectodermal cells that express proneural proteins. To reinforce the singularity, lateral inhibition through the Delta/Notch system and feedback regulations lead to exclusive expression of proneural proteins in SOPs. As transcriptional activators, proneural proteins execute a genetic program in SOP cells for the development of an eventually ES organ. In this article, we will summarize recent advances on how transcriptional regulation, protein degradation, endocytosis and gene silencing by microRNA participate in SOP specification.