Neurons are faced with the formidable challenge of having to assemble most of their cytoskeleton at axonal sites far removed from the protein synthetic machinery in the perikaryon. Their achievement seems all the more impressive now that new evidence is showing that the cytoskeleton may vary markedly in size and composition along the axon and exhibit striking regional specializations. Further complexity is contributed to this structure by a growing assortment of cytoskeleton-associated proteins that cross-link the various fibrous elements and stabilize cytoskeletal architecture. Much of the dynamic behavior of cytoskeletal proteins and polymers in axons is locally controlled. This regulation involves, in part, a system of protein kinases and phosphatases modulated by both intercellular and intracellular signals. Conceptual models of slow axonal transport have evolved to accommodate these new findings.