Regeneration of infarcted heart muscle remained a dream of modern medicine despite of comprehensive research on stem cell and gene therapy. Both technologies have not gained broad clinical use due to limited clinical results and significant side-effects including tumor formation. Shockwave therapy induces tissue regeneration in infarcted heart muscle and thereby significantly improves heart function (left ventricular ejection fraction). Shockwaves at low-energy levels are in broad clinical use for tissue regeneration in other indications, mainly in orthopedics (see International Society of Medical Shockwave Treatment – www.ismst.com). It is therefore proven safe in millions of patients over more than 30 years. This distinguishes shockwave therapy clearly from all other regenerative therapy approaches! While establishing cardiac shockwave therapy for the intraoperative use in cardiac surgery we are in parallel developing a second generation heart applicator for minimally-invasive/ interventional use in cardiology.