Mechanical ventilation (MV) has been an integral method used in ICU care for decades. MV is typically viewed as a life-supporting intervention. However, it can also contribute to lung injury through stress and strain, as evidenced by ventilator-induced lung injury (VILI), even in previously healthy lungs. The negative impact may be worsened when significant lung non-homogeneity is present, eg. ALI and ARDS. Protective lung strategies to minimize VILI are to use low tidal volumes (Vt 4–6 mL/kg/PBW), plateau pressures (P
plat
) <30 cmH
2
O and relatively high positive end-expiratory pressures (PEEP). Yet, use of constantly high PEEP levels is well recognized to result in hemodynamic compromise of the right ventricle, increased stress and strain through high mechanical energy impact on the lung and overdistension of relatively healthy lung tissue. Taking these issues into consideration, a different approach to mechanical ventilation was developed specifically for patients with non-homogeneity. This review focuses on a feature called programmed multi-level ventilation (PMLV). It is not a ventilation mode per se, but rather a form of extension that adjusts and modifies any ventilation mode (eg PCV,PSV, VCV, SIMV, etc.). PMLV is based on measured time constants (Tau) of the whole respiratory system, including artificial airways, breathing circuits, humidification devices and mechanical ventilator. Using a physiology-based approach presents a method to ventilate non-homogenous lungs through cyclic changes of different PEEP levels; recruitment takes place in lung areas with long time constants but protects relatively healthy lung areas from overdistension thus minimizing excessive mechanical power to the lung tissue.