Recently, cold atmospheric pressure plasmas (CAPs) have provided many new opportunities in dermatology by providing a multimodal action of reactive agents (RA). This review critically examines the generation, transport, and physical effects induced by CAPs in dermatologic treatments. We introduce the most suitable plasma sources, which provide a multitude of physical effects on the skin without any electric or thermal shocks. The mechanisms of generation and transport of the key reactive species are introduced and examined from the viewpoint of their applications in dermatology. Special attention is paid to study the “plasmaporation” effect, which enables RA penetration through healthy and damaged skin. Plausible physical mechanisms involved in the CAP treatment of some of the most common skin diseases are analyzed.