With the increase in the global prevalence of obesity, there is a parallel rise in the proportion of obese patients admitted to intensive care units, referred for major surgery or requiring long-term non-invasive ventilation (NIV) at home for chronic respiratory failure. We describe the physiological effect of obesity on the respiratory system mainly in terms of respiratory mechanics, respiratory drive, and patency of the upper airways. Particular attention is given to the prevention and the clinical management of respiratory failure in obese patients with a main focus on invasive and NIV in intensive care during the perioperative period and long-term use of NIV on return home. We also address other aspects of care of obese patients, including antibiotic dosing and catheter-related infections.