ALS is a devastating neurological disease causing progressive and relentless paralysis over months to years until death from respiratory failure. ALS kills 1 in every 300 people and is the commonest reason to seek assisted suicide. The aim of the STRENGTH consortium is to identify factors that affect susceptibility to ALS or modify the pattern of ALS onset or survival duration as targets for the development of new therapies. Until now, the usual approach has been to consider ALS as a homogeneous disease and identify genetic or environmental risk factors. STRENGTH uses a novel approach, first using clinical, laboratory and sophisticated clustering methods to identify homogeneous patient subgroups to increase power, and second using multiple layers of data from environmental questionnaires and genetics from the same individuals enrolled in pan-European population registers covering a population of about 120 million people, to identify for the first time how risk and protective factors work in concert to cause and modify ALS. In addition, STRENGTH partners include epigeneticists, able to develop this field in ALS and to further reveal the interface between genetic and environmental interaction. STRENGTH capitalises on existing infrastructure from the EU funded EuroMOTOR project which enables collection of large data sets, and the JPND funded SOPHIA project which ensures the data collection follows standard operating procedures throughout Europe, and will enable the discovery of new pharmaceutical targets for ALS.