In the past, the use of face masks in western countries was essentially limited to occupational health. Now, because of the COVID-19 pandemic, mask-wearing has been recommended as a public health intervention. As potential side effects and some contraindications are emerging, we reviewed the literature to assess the impact of them in daily life on patient safety and to provide appropriate guidelines and recommendations. We performed a systematic review of studies investigating physiological impact, safety, and risk of masks in predefined categories of patients, which have been published in peer-reviewed journals with no time and language restrictions. Given the heterogeneity of studies, results were analyzed thematically. We used PRISMA guidelines to report our findings. Wearing a N95 respirator is more associated with worse side effects than wearing a surgical mask with the following complications: breathing difficulties (reduced FiO 2 , SpO 2 , PaO 2 increased ETCO 2 , PaCO 2 ), psychiatric symptoms (panic attacks, anxiety) and skin reactions. These complications are related to the duration of use and/or disease severity. Difficulties in communication is another issue to be considered especially with young children, older person and people with hearing impairments. Even if benefits of wearing face masks exceed the discomfort, it is recommended to take an “air break” after 1–2 h consecutively of mask-wearing. However, well-designed prospective studies are needed. The COVID-19 pandemic could represent a unique opportunity for collecting large amount of real-world data. Supplementary Information The online version contains supplementary material available at 10.1007/s11739-022-03083-w.