Disease outbreaks are adverse events which can occur in any healthcare setting and pose a threat to patient safety and lives. Regardless of scope, an investigation of a potential outbreak involves certain predictable epidemiological elements. Each inquiry requires a systematic approach to verification of diagnosis, formation of a case definition, creating a line list, preparing an epidemic curve of disease distribution, and implementing infection prevention and control measures. Communication and mutual cooperation between the healthcare team, public health experts, and the infection preventionists lead to effective management. The ultimate goal of any outbreak investigation is to promptly identify problematic pathogens, stop ongoing disease transmission, and reduce risks for future events.