Abstract Chronic and latent infections, characterized by the persistence of pathogens in hidden reservoirs within the human body, represent a profound and often overlooked challenge to long-term health and healthspan. Conventional antimicrobial therapies often fail to eradicate these reservoirs, leading to recurrent infections, chronic inflammation, and accelerated age-related decline. This paper proposes a paradigm shift in infection management: Therapeutic Hyperthermia for Reservoir Disruption. We hypothesize that precisely controlled, localized heat application can disrupt pathogen reservoirs, weaken biofilm protection, directly inactivate pathogens, and stimulate localized immune responses, thereby facilitating pathogen clearance and enhancing human healthspan. We explore the mechanistic underpinnings of this novel therapeutic approach, outline advanced technologies for targeted and safe heat delivery, review preclinical evidence supporting its efficacy, and discuss the transformative potential of therapeutic hyperthermia to address the unmet needs of reservoir-associated infections and promote a new era of proactive healthspan extension in the 21st Century.