Despite the high prevalence of clinical pathways (CPWs), the results from published studies are inconsistent and contradictory. The plethora of study designs, settings and lack of an agreed definition of a CPW make the relevance of individual studies difficult to apply to clinical settings. It was timely to catalogue and analyse the existing evidence base for CPWs via a rigorous systematic review. Systematic reviews and meta-analyses provide a high level of evidence for the effectiveness of interventions and are commonly employed reviewing strategies for addressing scientific questions in health-related research. This method is especially useful when research results are known to be inconsistent. Instead of conducting another primary evaluation, a detailed review is needed that reflects a summation of available research. This paper reports and discusses methodological and technical issues of a systematic review of the effectiveness of CPWs in hospitals, based on our experience with the Cochrane Effective Practice and Organisation of Care Group.