Methemoglobinemia is a rare pathology that results from the oxidation of iron in the hemoglobin molecule. Oxidation of iron switches it from the ferrous to the ferric state, and impedes the ability of hemoglobin to carry oxygen. Hence, methemoglobinemia often results in hypoxemia. The disease can be hereditary or acquired, and its diagnosis can be challenging. This rare condition may often be missed by clinicians, since information on oxygen saturation provided by standard pulse oximeters is unreliable. We here present two cases of acquired methemoglobinemia. The first one is a 24-year old woman, who received dapsone as an alternative antibiotic therapy because of known allergies to a series of other antibiotics and who could not get weaned from mechanical ventilation despite minimal ventilator support. The second case describes a 49-year old man who developed respiratory insufficiency following the use of 'poppers' containing alkyl nitrites. Following treatment of both patients using the antidote methylene blue, they could be successfully weaned from mechanical ventilation.