Exercise represents a dynamic integration of rapidly activated respiratory, cardiovascular and musculoskeletal responses to meet rising metabolic demands. While the human body has a remarkable ability for exertion and endurance, in disease states, and particularly in respiratory disease, these mechanisms are often compromised, resulting in dyspnoea and reduced exercise tolerance. This review outlines normal exercise physiology, including cardiac, ventilatory and skeletal muscle adaptations to enhance oxygen uptake and delivery to working muscle, and examines how these are altered in conditions such as asthma, chronic obstructive pulmonary disease, interstitial lung disease and pulmonary hypertension. Key management considerations are highlighted to support and optimise functional capacity in patients suffering from these conditions. The unique challenges of exercise, with and without respiratory disease, in specific contexts - including underwater diving, high altitude exposure, and pregnancy - are also discussed. We briefly review policies and prohibitions on medications for competitive athletes with respiratory disease, where adherence to anti-doping regulations, especially regarding inhaled beta-agonists and corticosteroids, is crucial. Overall, understanding the physiological basis for exercise limitation enables clinicians to be more effective in their assessment, therapeutic intervention and counselling for patients seeking to maintain activity and quality of life despite respiratory compromise.