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Mask ventilation is the most fundamental skill in airway management. In this review, we summarize the current knowledge about difficult mask ventilation (DMV) situations. Various definitions for DMV have been used in the literature. The lack of a precise standard definition creates a problem for studies on DMV and causes confusion in data communication and comparisons. DMV develops because of multiple factors that are technique related and/or airway related. Frequently, the pathogenesis involves a combination of these factors interacting to cause the final clinical picture. The reported incidence of DMV varies widely (from 0.08% to 15%) depending on the criteria used for its definition. Obesity, age older than 55 yr, history of snoring, lack of teeth, the presence of a beard, Mallampati Class III or IV, and abnormal mandibular protrusion test are all independent predictors of DMV. These signs should, therefore, be recognized and documented during the preoperative evaluation. DMV can be even more challenging in infants and children, because they develop hypoxemia much faster than adults. Finally, difficult tracheal intubation is more frequent in patients who experience DMV, and thus, clinicians should be familiar with the corrective measures and management options when faced with a challenging, difficult, or impossible mask ventilation situation.