Filtering facepiece respirators (FFRs) are recommended for use as precautions against airborne pathogenic microorganisms; however, during pandemics demand for FFRs may far exceed availability. Reuse of FFRs following decontamination has been proposed but few reported studies have addressed the feasibility. Concerns regarding biocidal efficacy, respirator performance post decontamination, decontamination cost, and user safety have impeded adoption of reuse measures. This study examined the effectiveness of three energetic decontamination methods [ultraviolet germicidal irradiation (UVGI), microwave-generated steam, and moist heat] on two National Institute for Occupational Safety and Health-certified N95 FFRs (3M models 1860s and 1870) contaminated with H5N1. An aerosol settling chamber was used to apply virus-laden droplets to FFRs in a method designed to simulate respiratory deposition of droplets onto surfaces. When FFRs were examined post decontamination by viral culture, all three decontamination methods were effective, reducing virus load by > 4 log median tissue culture infective dose. Analysis of treated FFRs using a quantitative molecular amplification assay (quantitative real-time polymerase chain reaction) indicated that UVGI decontamination resulted in lower levels of detectable viral RNA than the other two methods. Filter performance was evaluated before and after decontamination using a 1% NaCl aerosol. As all FFRs displayed <5% penetration by 300-nm particles, no profound reduction in filtration performance was caused in the FFRs tested by exposure to virus and subsequent decontamination by the methods used. These findings indicate that, when properly implemented, these methods effectively decontaminate H5N1 on the two FFR models tested and do not drastically affect their filtering function; however, other considerations may influence decisions to reuse FFRs.