Myelination facilitates the transmission of electrical signals along axons and ensures their long-term viability, and most axons in the central nervous system are eventually myelinated by oligodendrocytes. But are the timing and extent of myelination regulated by the intrinsic properties of oligodendrocytes or by axons? To address this question, David Lyons and colleagues examine myelination by single oligodendrocytes in vivo in zebrafish (see p. 4443). As in mammals, zebrafish oligodendrocytes myelinate either a few large caliber axons or numerous smaller axons, they report. They further show that the large caliber Mauthner axon is the first axon to be myelinated. Then, using two independent genetic manipulations, the researchers generate zebrafish that have additional Mauthner axons. In these fish, oligodendrocytes that typically myelinate one Mauthner axon in wild-type fish myelinate multiple Mauthner axons, and oligodendrocytes that exclusively myelinate smaller caliber axons in wild-type fish also myelinate the supernumerary Mauthner axons. Thus, the researchers conclude, individual axons regulate the myelinating potential of single oligodendrocytes.