Translational neuroscience is in the doldrums. The stroke research community was among the first to recognize that the motivations inherent in our system of research can cause investigators to take shortcuts, and can introduce bias and reduce generalizability, all of which leads ultimately to the recurrent failure of apparently useful drug candidates in clinical trials. Here, we review the evidence for these problems in stroke research, where they have been most studied, and in other translational research domains, which seem to be bedevilled by the same issues. We argue that better scientific training and simple changes to the way that we fund, assess and publish research findings could reduce wasted investment, speed drug development, and create a healthier research environment. For 'phase III' preclinical studies--that is, those studies that build the final justification for conducting a clinical trial--we argue for a need to apply the same attention to detail, experimental rigour and statistical power in our animal experiments as in the clinical trials themselves.