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Dyspnea is the highly threatening experience of breathlessness experienced by patients with diverse pathologies, including respiratory, cardiovascular, and neuromuscular diseases, cancer and panic disorder. This debilitating symptom is especially prominent in the elderly and the obese, two growing populations in the Western world. It has further been found that women suffer more strongly from dyspnea than men. Despite optimization of disease-specific treatments, dyspnea is often inadequately treated. The immense burden faced by patients, families and the healthcare system makes improving management of chronic dyspnea a priority. Dyspnea is a multidimensional sensation that encompasses an array of unpleasant respiratory sensations that vary according to underlying cause and patient characteristics. Biopsychological factors beyond disease pathology exacerbate the perception of dyspnea, increase symptom severity and reduce quality of life. Psychological state (especially comorbid anxiety and depression), hormone status, gender, body weight (obesity) and general fitness level are particularly important. Neuroimaging has started to uncover the neural mechanisms involved in the processing of sensory and affective components of dyspnea. Awareness of biopsychological factors beyond pathology is essential for diagnosis and treatment of dyspnea. Increasing understanding the interactions between biopsychological factors and dyspnea perception will enhance the development of symptomatic treatments that specifically address each patient's most pressing needs at a specific stage in life. Future neuroimaging research can provide objective markers to fully understand the role of biopsychological factors in the perception of dyspnea in the hope of uncovering target areas for pharmacologic and non-pharmacologic therapy.