Healthcare personnel often find themselves on the frontlines of any epidemic, and may be at particularly high risk of acquiring respiratory viral illnesses when compared to the general population. Many aspects dictate how respiratory viruses spread both inside the hospital and out: Elements to consider include the specific type of virus being targeted for prevention, as well as environmental conditions and host factors, such as age and immune status. Due to the diverse nature of these agents, multiple modes of transmission, including contact, droplet, aerosol, and transocular, must be considered when designing an effective infection prevention program. In this review, we examine the data behind current theories of respiratory virus transmission and key elements of any respiratory illness prevention program. We also highlight other influences that may come into play, such as the cost-effectiveness of choosing one respiratory protection strategy over another.