Cold atmospheric pressure plasma has been proposed for sterilization of inert surfaces and disinfection of living tissues. Our recent studies reveal that chemically active species such as reactive oxygen species generated by a low-power atmospheric pressure non- thermal plasma source obtained by ionizing helium gas mixed with ambient air are mandatory for their antimicrobial effects. In addition, they also initiate intracellular signaling pathways required for wound healing in eukaryotic cells. Thus, exposure to plasma sustains healing of tissue injuries both indirectly through microbicidal effects and directly by action on cells such as fibroblasts involved in tissue regeneration.