The molecular basis of CD4:CD8 lineage commitment, in particular the mechanism by which the precise correlation between lineage choice and T-cell receptor (TCR) specificity toward class I or II major histocompatibility complex is achieved, remains controversial. Both stochastic/selective and instructive models in various forms have been proposed to explain this correlation. The two main experimental approaches previously employed to elucidate this process have focused on the beginning and end of the process, i.e. the influence of TCR signaling and the alternate transcriptional control of the CD4 and CD8 loci during commitment. The recent finding that the transcription factor Th-POK is necessary and sufficient for CD4 commitment has now provided a direct entry point for studying the intracellular pathways that govern lineage commitment. Here, we review data leading to the identification and characterization of this factor and discuss the implications of these studies in the context of current models of lineage commitment.