Three years after the beginning of the COVID-19 pandemic, better knowledge on the transmission of respiratory viral infections (RVI) including the contribution of asymptomatic infections encouraged most healthcare centers to implement universal masking. The evolution of the SARS-CoV-2 epidemiology and improved immunization of the population call for the infection and prevention control community to revisit the masking strategy in healthcare. In this narrative review, we consider factors for de-escalating universal masking in healthcare centers, addressing compliance with the mask policy, local epidemiology, the level of protection provided by medical face masks, the consequences of absenteeism and presenteeism, as well as logistics, costs, and ecological impact. Most current national and international guidelines for mask use are based on the level of community transmission of SARS-CoV-2. Actions are now required to refine future recommendations, such as establishing a list of the most relevant RVI to consider, implement reliable local RVI surveillance, and define thresholds for activating masking strategies. Considering the epidemiological context (measured via sentinel networks or wastewater analysis), and, if not available, considering a time period (winter season) may guide to three gradual levels of masking: (i) standard and transmission-based precautions and respiratory etiquette, (ii) systematic face mask wearing when in direct contact with patients, and (iii) universal masking. Cost-effectiveness analysis of the different strategies is warranted in the coming years. Masking is just one element to be considered along with other preventive measures such as staff and patient immunization, and efficient ventilation.