This review examined factors that delay thrombolysis and what management strategies are currently employed to minimise this delay, with the aim of suggesting future directions to overcome bottlenecks in treatment delivery.A systematic review was performed according to PRISMA guidelines. The search strategy included a combination of synonyms and controlled vocabularies from Medical Subject Headings (MeSH) and EmTree covering brain ischemia, cerebrovascular accident, fibrinolytic therapy and Alteplase. The search was conducted using Medline (OVID), Embase (OVID), PubMed and Cochrane Library databases using truncations and Boolean operators. The literature search excluded review articles, trial protocols, opinion pieces and case reports. Inclusion criteria were: (1) The article directly related to thrombolysis in ischaemic stroke, and (2) The article examined at least one factor contributing to delay in thrombolytic therapy.One hundred and fifty-two studies were included. Pre-hospital factors resulted in the greatest delay to thrombolysis administration. In-hospital factors relating to assessment, imaging and thrombolysis administration also contributed. Long onset-to-needle times were more common in those with atypical, or less severe, symptoms, the elderly, patients from lower socioeconomic backgrounds, and those living alone. Various strategies currently exist to reduce delays. Processes which have achieved the greatest improvements in time to thrombolysis are those which integrate out-of-hospital and in-hospital processes, such as the Helsinki model.Further integrated processes are required to maximise patient benefit from thrombolysis. Expansion of community education to incorporate less common symptoms and provision of alert pagers for patients may provide further reduction in thrombolysis times.