Microtubules are dynamic components of the cytoskeleton that are critical for the normal structure, function, and survival of neurons. They provide the major tracks for intracellular transport and local cues for positioning of mitochondria and other organelles; microtubules also interact with actin microfilaments to generate intracellular forces for both cell migration and dynamics of dendrites and axons, both during development and in response to synaptic activity. Microtubules are polymers composed of tandem repeats of α-β tubulin heterodimers; these heterodimers arrange to form a sheath of protofilaments and eventually a hollow tube. Microtubules are dynamically unstable and undergo periods of growth, shrinkage, and rest, depending on the continuous balance between filament assembly and disassembly. There are several groups of proteins that interact with microtubules. Important examples are the microtubule-associated protein tau, which promotes microtubule stabilization and bundling, and motor proteins such as kinesin and the dynein. Microtubule-based transport is essential for neuronal function. The specificity, directionality, and delivery of neuronal cargos via microtubule-based transport depend on local microtubule cues, as well as the opposing activity of kinesin and dynein motors. Genetic or neurodegenerative disorders affecting microtubules or their associated proteins produce a wide variety of clinical manifestations. For example, mutations in α- or β-tubulin are linked to developmental disorders such as lissencephaly; mutations affecting kinesin, dynein, or dynactin produce axonal neuropathies and motor neuron disease. Abnormal accumulations of hyperphosphorylated tau have been directly linked to several neurodegenerative tauopathies manifested with dementia, parkinsonism, or both. All these topics have been the subject of several reviews.1–10