Recent studies have shown both beneficial and detrimental effects of patient breathing effort in mechanical ventilation. Quantification of breathing effort may allow the clinician to titrate ventilator support to physiological levels of respiratory muscle activity. In this review we will describe the physiological background and methodological issues of the most frequently used methods to quantify breathing effort, including esophageal pressure measurement, the work of breathing, the pressure-time-product, electromyography and ultrasound. We will also discuss the level of breathing effort that may be considered optimal during mechanical ventilation at different stages of critical illness.