Preventing transmission of emerging infectious diseases remains a challenge for infection prevention and occupational safety programs. The recent Ebola and measles outbreaks highlight the need for pre-epidemic planning, early identification, and appropriate isolation of infected individuals and health care personnel protection. To optimally allocate limited infection control resources, careful consideration of major modes of transmission, the relative infectiousness of the agent, and severity of the pathogen-specific disease are considered. A framework to strategically approach pathogens proposed for health care settings includes generic principles (1) elimination of potential exposure, (2) implementation of administrative controls, (3) facilitation of engineering and environmental controls, and (4) protection of the health care worker and patient using hand hygiene and personal protective equipment. Additional considerations are pre-epidemic vaccination and incremental costs and benefits of infection prevention interventions. Here, major strategies for preventing health-care-associated transmissions are reviewed, including reducing exposure; vaccination; administrative, engineering, and environmental controls; and personal protective equipment. Examples from recent outbreaks are used to highlight key infection prevention aspects and controversies.