Dyspnea is a subjective and nonspecific symptom, yet very distressing for those who experience it. Acute onset dyspnea and exacerbation of chronic dyspnea from heart or lung disease significantly add to the number of emergency department visits and inpatient admissions. Although dyspnea may appear to be a simple condition to evaluate and manage, it is actually complex in description and quality. As such, dyspnea is the first symptom of many diseases. The onset of dyspnea can be due to a new acute disease, the exacerbation of an existing chronic illness, or a new disease compounding a chronic illness. Finding the cause of dyspnea is generally more difficult than it originally may appear. Therefore, the purpose of this article is to discuss the differential diagnoses associated with dyspnea.