One could be forgiven for thinking that the only road to evidence-based clinical practice is the application of results from randomised controlled trials (or systematic reviews of such). By contrast, single-subject designs in the context of evidence-based clinical practice are believed by many to be strange bedfellows. In this paper, we argue that single-subject designs play an important role in evidence-based clinical practice. We survey the contents of Neuropsychological Rehabilitation in relation to single-subject designs and tackle the main criticisms that have been levelled against them. We offer practical guidance for rating the methodological quality of single-subject designs and applying statistical techniques to measure treatment efficacy. These guides are equally applicable to research studies and everyday clinical practice with individual patients.