Respirators are widely used for protection against inhaled toxins. The emphasis of research and implementation effort has evolved through several stages: the respirator device itself, use situation, respirator program factors under employer control, individual worker factors not under employer control, and occupational health systems. For this study, a computer-simulation decision assistance model was developed to assess the impact of various factors on the number of workers receiving adequate protection. Factors include the respirator protection factor, identification of sites needing respirator protection, selection of proper device, availability when needed, frequency of ever use, regularity of use among users, and variability in personal susceptibility or other factors. This analysis demonstrates that for both moderate-risk and high-risk (ie, IDLH, immediately dangerous to life and health) exposures under current circumstances, the actual protection afforded depends upon the optimization of program factors and detection of atypical outlier persons and worksites. Therefore, programs and research must focus on these areas. Occupational medicine specialists should help optimize these areas and, in addition, use each case of respiratory protection failure as an index case to improve the overall programs.