This review discusses the potential of ultraviolet C (UVC) irradiation as an alternative approach to current methods used to treat localized infections. It has been reported that multidrug-resistant microorganisms are equally sensitive to UVC irradiation as their wild-type counterparts. With appropriate doses, UVC may selectively inactivate microorganisms while preserving viability of mammalian cells and, moreover, is reported to promote wound healing. UVC is also found in animal studies to be less damaging to tissue than UVB. Even though UVC may produce DNA damage in mammalian cells, it can be rapidly repaired by DNA repair enzymes. If UVC irradiation is repeated excessively, resistance of microorganisms to UVC inactivation may develop. In summary, UVC should be investigated as an alternative approach to current methods used to treat localized infections, especially those caused by multidrug-resistant microorganisms. UVC should be used in a manner such that the side effects would be minimized and resistance of microorganisms to UVC would be avoided.