Contrast-enhanced ultrasound is based on the detection of acoustically-active microbubbles. Intravital microscopy has demonstrated that these contrast agents are confined to the vascular space and that their rheologic profile is similar to that of erythrocytes. Hence, these agents are ideal tracers for evaluating microvascular perfusion. The ability to parametrically non-invasively evaluate blood flux rate through tissue and absolute microvascular blood volume has also proved to be a valuable asset for evaluating complex microvascular adaptations in health and disease. This presentation will focus on how contrast-enhanced ultrasound data has been used to evaluate: (1) complex vascular adaptations to coronary and/or peripheral stenosis, (2) rheologic abnormalities associated with hyperlipidemia or other diseases of red cell deformability, (3) mechanism of effect of certain medications aimed at improving capillary flow, (4) capillary adapations in diabetes mellitus, and (5) angiogenic response in ischemia and tumors.