Medical practitioners have always relied on surrogate markers to make their diagnosis; the pallor of shock, the flush of inflammation. But although current methods are more sophisticated, and the impetus to discover reliable and accurate biomarkers for early detection are compelling, the stable of available biomarkers for the early diagnosis of cancer is still dominated by a handful of markers first discovered decades ago. This publication/title is dedicated to one fresh approach to the discovery and validation of disease biomarkers, loosely termed the ‘systems biology of biomarkers’. What sets it apart from other, more traditional, approaches is both the types of data used and the tools used for data analysis. The seven articles published here describe the concept of systems biomedicine and explore some of the novel strategies and approaches being employed in current research. The process of identifying biomarkers for cancer can be likened to the process of threat detection in the defence arena. The defence community has responded by adopting ‘composite signatures’ of threat which employ multidimensional datasets, in which each dimension employs a different measurement or technique. According to the editors of this volume, it might be time for biomedical scientists to employ the same strategy. Systems biology can provide the tools to build, test and validate a composite signature of disease.