Plasma is referred to as the fourth state of matter and is frequently generated in the environment of a strong electric field. The result consists of highly reactive species--ions, electrons, reactive atoms and molecules, and UV radiation. Plasma Medicine unites a number of fields, including Physics, Plasma Chemistry, Cell Biology, Biochemistry, and Medicine. The treatment modality utilizes Cold Atmospheric Plasma (CAP), which is able to sterilize and treat microbes in a nonthermal manner. These gas-based plasma systems operate at close to room temperature and atmospheric pressure, making them very practical for a range of potential treatments and are highly portable for clinical use throughout the health care system. The hypothesis is that gas based plasma kills bacteria, fungus, and viruses but spares mammalian cells. This paper will review systematic work which shows examples of systems and performance in regards to antimicrobial effects and the sparing of mammalian cells. The mechanism of action will be discussed, as well as dosing for the treatment of microbial targets, including sterilization processes, another important healthcare need. In addition, commercial systems will be overviewed and compared, along with evidence-based, patient results. The range of treatments cover wound treatment and biofilms, as well as antimicrobial treatment, with little chance for resistance and tolerance, as in drug regimens. Current clinical studies include applications in dentistry, food treatment, cancer treatment, wound treatment for bacteria and biofilms, and systems to combat health care related infections.