Scientists have known for many years that our risks of developing different diseases are due to the complex interplay of different factors: our lifestyle and environment; our personal susceptibility; and the play of chance. But, despite this longstanding awareness, a clear picture of the combined effects of different factors on the risks of different diseases in different circumstances is yet to emerge. For the comprehensive and reliable quantification of the combined effects of lifestyle, environment, genotype and other exposures, prospective studies have a number of advantages. As well as allowing effects on a wide range of different conditions to be studied, exposures can be assessed prior to disease development, which avoids recall bias and allows investigation of factors that might be affected by disease processes and treatments, or an individual's response to developing some condition. Prospective studies are also able to assess those conditions that cannot readily be investigated retrospectively and can include all cases that have high fatality rates. Cohorts to date have typically been characterised by small numbers of disease cases (which may yield unstable estimates due to random variations), incomplete or inadequate measures of potential risk factors (which may yield systematic under-estimates of disease associations) and incomplete or inadequate measures of confounding factors (which may yield over- or under-estimates). Consequently, to help assess the main causes of various chronic diseases quantitatively, there is a strategic need to establish some large blood-based prospective studies of well phenotyped individuals, with prolonged and detailed follow-up of cause-specific morbidity and mortality.