The eukaryotic cytoskeleton is composed of filamentous structures, namely microfilaments, microtubules and intermediate filaments. The cytoskeleton is an essential component of cells due to its rote in various cellular functions, such as intracellular transport, organelle positioning, chromosome segregation and cytokinesis. Abnormalities in cytoskeleton, as well as associated proteins and regulatory pathways, have been shown to contribute to disease pathomechanisms including cancer and neurodegenerative diseases. Therefore, cytoskeleton is an important therapeutic target and many compounds have been identified or developed to modulate the cytoskeleton. In this review, we focused on cytoskeleton modulatory compounds and summarized their mechanisms of action.