There are approximately 5,700 hospitals in the United States, 3,000-4,000 that are antiquated or obsolescing. To meet increased service demands, remain financially viable; meet needs to upgrade aging infrastructure and incorporate medical and technology advancements, healthcare facilities are in a perpetual state of construction. Outbreaks of nosocomial infections have historically been documented in association with construction and renovation actives within health care facilities. For most healthy individuals, environmental exposures to etiological agents, results in no adverse effects but in immune-compromised patient, they are left susceptible to inadvertent exposures during construction to opportunistic bacteria, fungi and viruses. Evidence scientifically linking construction work and nosocomial infections as well as the efficacy and clinical relevance of infection control precautions is somewhat lacking but the empirical evidence and recommendations to support protective measures is steadily growing. Opening a "Pandora's Box" during construction can unleash unintended consequences therefore; it is imperative that a thorough, multidisciplinary approach towards an infection control plan is put clearly and firmly in place allowing health care construction projects to move forward with confidence that patient safety is the first specification.