Non-invasive ventilation (NIV) has dramatically changed the treatment of both acute and chronic respiratory failure in the last 2 decades. The success of NIV is correlated to the application of the “best ingredients” of a patient’s “tailored recipe,” including the appropriate choice of the selected candidate, the ventilator setting, the interface, the expertise of the team, and the education of the caregiver. The choice of the interface is crucial for the success of NIV. Type (oral, nasal, nasal pillows, oronasal, hybrid mask, helmet), size, design, material and headgears may affect the patient’s comfort with respect to many aspects, such as air leaks, claustrophobia, skin erythema, eye irritation, skin breakdown, and facial deformity in children. Companies are paying great attention to mask development, in terms of shape, materials, comfort, and leak reduction. Although the continuous development of new products has increased the availability of interfaces and the chance to meet different requirements, in patients necessitating several daily hours of NIV, both in acute and in chronic home setting, the rotational use of different interfaces may remain an excellent strategy to decrease the risk of skin breakdown and to improve patient’s tolerance. The aim of the present review was to give the readers a background on mask technology and materials in order to enhance their “knowledge” in making the right choice for the interface to apply during NIV in the different clinical scenarios.