Stroke thrombolysis has emerged as a valuable treatment for acute ischaemic stroke in the first 4.5 hours after symptom onset. The need for rapid initiation of treatment and the small but inherent risk of life-threatening side effects requires a high degree of diagnostic accuracy with only limited time for investigation. It is widely recognized that a significant proportion of patients presenting with “stroke-like” symptoms will in fact have an alternative diagnosis – so called stroke mimics. There has been anxiety that wrongful treatment of stroke mimics could be harmful. This paper reviews the published data on the incidence of stroke mimics and the outcome of thrombolysis in these cases. We conclude that the risk of adverse outcomes from thrombolysis in these cases appears to be minimal on the available evidence and is certainly significantly less than the potential harm that could result from denial of, or delay in administration of thrombolytic therapy.