Balneotherapy for humans has a long tradition in Germany. Carbonated water or CO2 containing spring water has been known for ancient times, not only in spas for bathing but also for drinking. In 1845 the German spa physician Dr. F. Bodo from Bad Nauheim noted a “congested, velvety reddened skin” after taking a bath in warm CO2 enriched water. Conducting absorption experiments Hediger in 1928 demonstrated for the first time that CO2 is absorbed into the body by passing through the intact skin. In Germany 80% of the natural mineral spas contain the minimum concentration of 400mg/kg CO2 required for treatment and 50% of all spas have a CO2 content higher than 1000 mg/kg which is required for the designation as carbon dioxide enriched water. The spa resorts Bad Nauheim and Bad Krozingen harbor natural mineral springs with the world wide highest CO2 concentrations containing 2600 mg/kg and 2200 mg/kg, respectively. These springs belong to artesian wells which means the spring water is under a hydrostatic pressure that is high enough to well up to the surface without any pumps.   The beneficial effects of CO2 balneotherapy are not known in detail yet. However, animal studies have shown that bathing in carbon dioxide rich water enhances collateral blood flow in ischemic hindlimb through mobilization of endothelial progenitor cells and activation of NO system. Daily CO2 bathing for 28 days induced a 4 fold increase in collateral vessel density which was prevented by the administration of L-NAME a NO inhibitor. In humans CO2 bathing improves arteriolar blood flow in patients with arterial occlusive diseases. Patients with necrosis of skin and soft tissue due to disturbed blood flow showed profound improvement of the skin defects with decrease of the necrosis area. To the skin CO2 enriched water has topical effects. Ten days of rinsing detergent-damaged skin with CO2 enriched water enhanced clinical skin regeneration, enhanced epidermal lipid synthesis and enhanced barrier repair. Taking together CO2 balneotherapy has different beneficial effects on human diseases. This review presents the effects of CO2 enriched water on humans diseases and discusses its clinical indications.