A mainstay of personal protective equipment (PPE) during the COVID-19 pandemic is the N95 filtering facepiece respirator. N95 respirators are commonly used to protect healthcare workers from respiratory pathogens, including the novel coronavirus SARS-CoV-2, and are increasingly employed by other frontline workers and the general public. Under routine circumstances, these masks are disposable, single-use items, but extended use and reuse practices have been broadly enacted to alleviate critical supply shortages during the COVID-19 pandemic. While extended-time single use presents a low risk of pathogen transfer, repeated donning and doffing of potentially contaminated masks presents increased risk of pathogen transfer. Therefore, efficient and safe decontamination methods for N95 masks are needed to reduce the risk of reuse and mitigate local supply shortages. Here we review the available literature concerning use of germicidal ultraviolet-C (UV-C) light to decontaminate N95 masks. We propose a practical method for repeated point-of-use decontamination using commercially-available UV-C crosslinker boxes from molecular biology laboratories to expose each side of the mask to 800–1200 mJ/cm2 of UV-C. We measure the dose that penetrated to the interior of the respirators and model the potential germicidal action on coronaviruses. Our experimental results, in combination with modeled data, suggest that a two-minute UV-C treatment cycle should induce a >3-log-order reduction in viral bioburden on the surface of the respirators, and a 2-log order reduction throughout the interior. We find that a dose 50-fold greater does not impair filtration or fit of 3M 8210 N95 masks, indicating that decontamination can be performed repeatedly. As such, UV-C germicidal irradiation (UVGI) is a practical strategy for small-scale point-of-use decontamination of N95s.