Background: Dyspnea is a common symptom experienced by many patients with chronic, life-threatening, and/or life-limiting illnesses. Although it can be defined and measured in several ways, dyspnea is best described directly by patients through regular assessment, as its burdens exert a strong influence on the patient's experience throughout the trajectory of serious illness. Its significance is amplified due to its impact on family and caregivers. Discussion: Anatomic and physiologic changes associated with dyspnea, and cognitive perceptions related to patients and the underlying disease, provide insights into how to shape interventions targeting this oppressive symptom. Additionally, as described in the concept of "total dyspnea," the complex etiology and manifestation of this symptom require multidisciplinary treatment plans that focus on psychological, social, and spiritual distress as well as physical components. Several validated assessment tools are available for clinical and research use, and choice of method should be tailored to the individual patient, disease, and care setting in the context of patient-centered care. Conclusion: This article, the first in a two-part series, reviews the identification and assessment of dyspnea, the burden it entails, and the underlying respiratory and nonrespiratory etiologies that may cause or exacerbate it.