Tropomyosin (Tm) belongs to a family of actin-associated proteins and multiple genes encode a range of highly similar isoforms. Together with various other actin-binding proteins, Tm defines the physical and biochemical properties of the actin cytoskeleton. The complex morphological alterations undertaken by neurons during development and maturation are complemented by the quantitative and qualitative changes in the expression of Tm isoforms. In addition, Tm isoforms define spatially and temporally distinct pools of actin microfilaments, identifying unique intracellular neuronal compartments. Genetic manipulation of Tm isoforms dramatically impacts on neuronal morphogenesis. Most importantly, the observed changes occur in an isoform and intracellular compartment-specific manner, further demonstrating the lack of redundancy among the isoforms. A hallmark of various neurodegenerative disorders is an abnormal cytoskeleton, characterized by the presence of neuronal inclusions composed of specific cytoskeletal components; among them Tm. The significance of the aberrant expression and localization of Tm in these neuronal diseases is yet to be determined but is likely to reflect differences in the involvement of different structural compartments in specific diseases.