To the Editor Lima et al1 recently reported that a transient decline in flow-mediated dilation (FMD) after mental stress is associated with adverse cardiovascular outcomes. This article highlights the ongoing use of FMD as an indirect bioassay of in vivo endothelial function. Endothelial dysfunction is an early and integral atherosclerotic event, and FMD assessment is noninvasive, accessible, and cheap. Nonetheless, FMD remains a research tool and has failed to make clinical primetime. The problem is not with the conceptual basis of applying a functional bioassay to assess endothelial function in vivo but rather that variability exists in the way the test is conducted and the data are analyzed.