The recent meta-analysis of NXY-059 in experimental stroke models using individual animal data found the drug to be an effective neuroprotective agent. However, the failure of translation of both this compound and many others from preclinical studies to the clinic indicates that new approaches must be used in drug discovery so that animal models become more reflective of the clinical situation, and studies using animal models of stroke mimic the design of studies performed in humans, as far as possible. In this review, we suggest that a fundamental paradigm shift is needed away from performing preclinical studies in individual laboratories to performing them in an organised group of independent laboratories. Studies should be run by a steering committee and should be supported by a coordinating centre, external data monitoring committee and outcome adjudication committee. This structure will mimic the practice of multicentre clinical trials. By doing so, future studies will minimise potential sources of bias including randomisation, concealment of allocation, blinding of surgery and outcome assessment and ensure publication of all data. It is likely that individual studies will involve increased heterogeneity and therefore will need to be larger. However, regular independent monitoring of data will allow development of interventions to be ceased immediately if neutral or negative data are obtained. The additional costs involved should be seen as reasonable when compared with the resources that would have been expended in running a clinical trial that subsequently proved negative.