Although dissolution of thrombus using ultrasound has been attempted for over 25 years, the clinical use of this technique remains limited. The ability of microbubbles to potentiate ultrasound-induced thrombolysis has renewed interest in this technique, which recanalizes occluded vessels without the need for fibrinolytic therapy. In this article, the potential mechanisms by which ultrasound and microbubbles produce thrombus dissolution are explored. In vitro and in vivo studies using ultrasound alone and ultrasound in combination with microbubbles to cause thrombolysis are reviewed. Potential clinical implications of more recent findings are explored.