Intracellular transport by microtubule-dependent motors is crucial for neuronal survival and function. Recent advances reveal novel strategies for the regulation of transport and the attachment of motors to cargoes. Current findings also illustrate the importance of directed transport in neuronal biology, including microtubule-motor-dependent transduction of neurotrophic signals and axonal damage signal complexes. Furthermore, recent data implicating the dysfunction of microtubule-dependent transport in the cause and development of several neurodegenerative diseases provides evidence for the vital role of transport in neuronal and organismal function.