The global increase in both coronary heart disease (CHD) and cardiovascular disease (CVD) and the associated increase in undetected subclinical cardiovascular pathology highlight the continuing need for improved risk prediction. Traditional risk factors fail to identify all ‘at-risk’ individuals. Although new risk factors, associated with endothelial function, inflammatory and oxidative stress pathways, for example, have been identified, studies have often observed only minimal improved risk classification when such markers are added. We examine the emerging evidence that short sleep may be a risk factor for obesity, type 2 diabetes and hypertension, and an independent predictor of stroke, CHD and CVD. We examine the underlying mechanisms and the evidence to suggest that short sleep may modulate the association between established factors and CVD. We consider whether the levels of markers of obesity and appetite control, energy metabolism, glucose homoeostasis, inflammation, thrombosis and haemostasis, which are affected by short duration of sleep, might be useful predictors of the risk of developing CVD. Finally, the usefulness of such markers for disease detection, management and prevention is considered.