Along with the global aging, the number of patients with cardiovascular disease complicated with various comorbidities is rapidly increasing. It has been demonstrated that repeated stimulation with sound waves stretches vascular endothelial cells and induces the expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF). Based on these findings, we were able to further demonstrate that physical stimulation by low-intensity shock wave or pulsed ultrasound (LIPUS) enhances phosphorylation of Erk1/2 and Akt via phosphorylation of Fyn and FAK, and subsequently induces the expression of eNOS and VEGF. Furthermore, we were able to develop a minimally invasive angiogenic therapy with sound waves, and have been performing both basic and clinical studies. In this article, we will briefly summarize the progress in our project of developing novel angiogenic therapies with sound waves.