Mechanical ventilation is a vital supportive therapy for critical care patients suffering from Acute Respiratory Distress syndrome (ARDS) or Acute Lung Injury (ALI) in view of oxygen supply. However, a number of associated complications often occur, which are collectively termed ventilator induced lung injuries (VILI) [1]. Biologically, these diseases manifest themselves at the alveolar level and are characterized by inflammation of the lung parenchyma following local overdistension or high shear stresses induced by frequent alveolar recruitment and derecruitment. Despite the more recent adoption of protective ventilation strategies based on the application of lower tidal volumes and a positive end-expiratory pressure (PEEP), patient mortality rates are with approximately 40% still very high. Understanding the reason why the lungs still become damaged or inflamed during mechanical ventilation is a key question sought by the medical community. In this contribution, an overview on recently developed building blocks of a comprehensive lung model will be given, with a main focus on lower airways.