Brain ischaemia leads to a cascade of biochemical events, many of which ultimately cause cell membrane injury. Therefore, measures aimed at protecting neuronal membranes could be useful treatment strategies following stroke. Citicoline (cytidine-5-diphosphocholine; CDP-choline) is a naturally occurring nucleotide derivative that may reduce central nervous system (CNS) ischaemic injury by stabilizing cell membranes and reducing free radical generation. Several animal models of ischaemic stroke or hypoxia have shown beneficial effects of citicoline treatment. Randomized clinical stroke treatment trials performed outside of the United States (US) have shown promising results but several recent US trials have failed to support the use of citicoline following middle cerebral artery (MCA) stroke. It remains possible that more specific subgroups of patients may benefit from this well tolerated therapy, but these subgroups have yet to be determined. In addition, there remains the possibility that efficacy may be seen when citicoline is administered in combination with other neuroprotectants with complementary mechanisms of action.