The vascular endothelium plays a pivotal role in modulating endothelial homeostasis. A number of methods have been developed to assess the function of this important tissue in humans in vivo, in the hope that such data may contribute to the early diagnosis and risk stratification of patients at risk for, or with, cardiovascular disease. Despite these efforts, a number of issues, both practical and theoretical, arise from the attempt of quantifying the elusive "endothelial function", and from the attempt of defining what is "endothelial dysfunction". The present paper, based on a lecture held at the conference of the European Society of Hemorheology and Microcirculation, will try to deal with these issues.