Cases of upper respiratory compromise that are characterized by inspiratory and/or expiratory noise and an increased effort to breathe warrant a thorough, systematic diagnostic evaluation. Compiling a complete history and performing a comprehensive physical examination are essential to establishing and prioritizing differential diagnoses. Extreme care needs to be taken when handling animals in this condition and all precautions to limit stress must be observed. The veterinarian should be prepared for all possible events and have the proper equipment readily available to perform endotracheal intubation or an emergency tracheostomy. The diagnostic plan for these animals should include a combination of the following: complete oral, pharyngeal, and laryngeal examinations; head and thoracic radiographs; abdominal and thoracic ultrasound; CT scan of the head and thorax; MRI of the head and thorax; rhinoscopy; and nasal cytology, biopsy, and histopathology. Depending on the final diagnosis, medical and/or surgical treatment may be necessary to ensure that the animal enjoys an appropriate quality of life. An illustration of these principles can be found in the following case report, which describes an adult, male castrated domestic shorthair cat with upper respiratory compromise.