Abstract A highly‐regulated and dynamic cytoskeleton is vital for functional cellular physiology and the maintenance of homeostasis. Although much is known about the mechanisms by which the cytoskeleton is regulated under physiological conditions, the effect of pathological stimuli and how this contributes to disease progression remains poorly understood. Hypoxia is a prominent microenvironmental feature of a range of pathological states including inflammation, cancer and ischaemia. In this review, we summarise what is known about the effects of hypoxia on the cytoskeleton and discuss the implications of this for physiology and disease. image