Chronic wound infections are a silent pandemic in danger of becoming a global healthcare crisis. Innovations to control infections and improve healing are required. In the context of this challenge, researchers are exploiting plasma-activated hydrogel therapy (PAHT) for use either alone or in combination with other antimicrobial strategies. PAHT involves the cold atmospheric pressure plasma activation of hydrogels with reactive oxygen and nitrogen species to decontaminate infections and promote healing. This opinion article describes PAHT for wound treatment and provides an overview of current research and outstanding challenges in translating the technology for medical use. A 'blueprint' of an autonomous PAHT is presented in the final section that can move the management and treatment of wounds from the clinical setting to the community.