Airborne transmission of infectious agents within indoor environments has been a recognized hazard for decades. Engineering controls such as ventilation and negative pressure have been helpful for control of airborne infectious agents in high-risk settings such as hospital isolation rooms. Increasing costs associated with providing ventilation has prompted renewed interest in other means to remove airborne infectious agents from room air, such as the application of ultraviolet germicidal irradiation (UVGI). One application of UVGI is to irradiate the air in the upper part of a room while minimizing radiation exposure to persons in the lower part of the room. Another application is to irradiate the air moving through ventilation ductwork. The aim of our research program, funded by grants from the CDC and Gilbert Foundation, is to systematically investigate the conditions under which UVGI can be expected to mitigate the spread of infectious agents. Results from detailed experiments conducted during the last 7 years will be discussed. In summary, upper-room UVGI is very effective at inactivating most species of airborne bacteria, but not fungi, at the levels provided to our test room. UVGI installed in ventilation ductwork can effectively inactivate both airborne bacteria and fungi at moderate air velocities, but not at high velocities due to reduced residence times.