Nitric oxide (NO) is involved in many biological functions and has been demonstrated to be important in wound healing. When delivered to a wound in its gaseous state, NO stimulates vasodilatation and angiogenesis, inhibits platelet and erythrocyte aggregation, reduces leukocyte adhesion, and is an important anti-inflammatory and antimicrobial agent. Many patients with chronic and hard-to-heal wounds have a deficiency of NO in their tissues ,which may contribute to slow and even arrested healing. However, it has been difficult to use NO for treatment because of its short half-life, which is measured in seconds. A recently developed device provides a way to generate NO and combine it with a stream of plasma energy, which extends its half-life to the point that it can provide a clinical effect. This device creates NO from the ambient air, and no other gases are needed. The combination of atmospheric oxygen and nitrogen at a high temperature generated by an electric arc results in NO and plasma energy (N2 + O2 = 2NO + 181 KJ energy). After generation, the NO/plasma energy-containing gas flow is cooled to 18-20°C, and NO is delivered to the tissues in a "dose" between 800 and 1000 ppm. When NO gas was combined with the plasma energy stream, the NO was found to penetrate intact skin or tissue up to 3cm to treat an underlying problem. Studies have shown that NO/plasma energy therapy promotes healing. This report summarizes current applications of this unique approach in the treatment of chronic, hard-to-heal and infected wounds.