Noninvasive positive-pressure ventilation (NPPV) has been used increasingly to treat acute respiratory failure (ARF). The best indications for its use are ARF in patients with COPD exacerbations, acute pulmonary edema, and immunocompromised states. For these indications, multiple controlled trials have demonstrated that therapy with NPPV avoids intubation and, in the case of COPD and immunocompromised patients, reduces mortality as well. NPPV is used to treat patients with numerous other forms of ARF, but the evidence is not as strong for its use in those cases, and patients must be selected carefully. The best candidates for NPPV are able to protect their airway, are cooperative, and are otherwise medically stable. Success is optimized when a skilled team applies a well-fitted, comfortable interface. Ventilator settings should be adjusted to reduce respiratory distress while avoiding excessive discomfort, patient-ventilator synchrony should be optimized, and adequate oxygenation should be assured. The appropriate application of NPPV in the acute care setting should lead to improved patient outcomes and more efficient resource utilization.