Cardiopulmonary bypass (CPB) is an integral component of cardiac surgery; however, one of its most critical complications is acute lung injury induced by multiple factors including systemic inflammatory response.The objective of this review is to investigate the multiple factors that can lead to CPB-induced lung injury. These include contact of blood components with the artificial surface of the CPB circuit, local and systemic inflammatory response syndrome (SIRS), lung ischemia/re-perfusion injury, arrest of ventilation, and circulating endotoxins. We also focus on possible interventions to curtail the negative impact of CPB, such as off-pump surgery, impregnation of the circuit with less biologically active substances, leukocyte depletion filters and ultrafiltration, and pharmacological agents such as steroids and aprotinin.Although many aspects of CPB are proposed to contribute to lung injury, its overall role is still not clear. Multiple interventions have been introduced to reduce the risk of pulmonary dysfunction, with many of these interventions having shown promising results, significantly attenuating inflammatory mediators and improving post-operative outcome. However, since lung injury is multifactorial and affected by inextricably linked components, multiple interventions tackling each of them is required.