While the angiographic appearance of coronary stenoses commonly directs interventional decisions, it may correlate imprecisely with hemodynamic or physiologic lesional significance. Previous data would suggest that direct measures of translesional physiology can be helpful in assessing the hemodynamic significance of stable coronary stenoses. In unstable ischemic syndromes, however, the hemodynamic severity of lesions may depend on the presence of variably occlusive intraluminal thrombus superimposed on fluctuating vessel tone. Under these circumstances, physiologic lesional assessment can yield helpful information, which nonetheless must be interpreted with caution in light of the clinical context. Determination of optimal management strategies for such patients remains difficult and must await further investigation of prognosis and outcome.