Recent developments in thrombolysis include transcutaneous ultrasound augmentation of tissue plasminogen activator (tPA) activity and microbubble augmented ultrasound lysis. While standard thrombolytic drugs are well-known, the increased thrombolytic drug activity with the addition of ultrasound is a new clinical tool early in development. The therapeutic thrombolytic action of ultrasonographic microbubble contrast agents and a beam of ultrasound when in contact with clot is also a technique rapidly developing and not widely appreciated. Both augmentation techniques have progressed to early clinical use. The use of directed ultrasound beams to increase lytic activity in a specific target with either technique may lead to fewer hemorrhagic complications, especially in anatomical areas remote from the target. The combination of intravenous tPA and directed ultrasound is very promising in the treatment of ischemic stroke in human trials, and microbubble augmented ultrasound thrombolysis has been proven effective in several animal models of stroke and clotted dialysis grafts, with phase I/II trials in human dialysis grafts, arteries, and veins ongoing. This paper will review the state-of-the-art in this rapidly progressing field.