The brains of many species demonstrate structural and functional bilateral asymmetry, yet the underlying molecular mechanisms are mostly unknown. In the Caenorhabditis elegans nervous system, the lineages arising from the two daughter cells of a particular blastomere known as ABarap produce a different cell on each side of the body: a motor neuron on the right and an epithelial cell on the left. Here, the authors show that the CAF-1 (chromatin assembly factor-1) protein complex, a histone chaperone that deposits histone H3 and H4 proteins onto replicating DNA, is required to establish this asymmetry, suggesting a role for epigenetic regulation in the generation of nervous system asymmetry.