Microtubules are one of the major cytoskeletal components of neurons, essential for many fundamental cellular and developmental processes, such as neuronal migration, polarity, and differentiation. Microtubules have been regarded as critical structures for stable neuronal morphology because they serve as tracks for long-distance transport, provide dynamic and mechanical functions, and control local signaling events. Establishment and maintenance of the neuronal microtubule architecture requires tight control over different dynamic parameters, such as microtubule number, length, distribution, orientations, and bundling. Recent genetic studies have identified mutations in a wide variety of tubulin isotypes and microtubule-related proteins in many of the major neurodevelopmental and neurodegenerative diseases. Here, we highlight the functions of the neuronal microtubule cytoskeleton, its architecture, and the way its organization and dynamics are shaped by microtubule-related proteins. The structural organization and dynamic remodeling of the cytoskeleton contributes to all morphological and functional changes in neurons. Here, Kapitein and Hoogenraad review the functions of the neuronal microtubule cytoskeleton and the mechanisms that drive its organization and dynamics.