PURPOSE OF REVIEW: Considerable progress has recently been made in understanding the modulation of acute lung injury by cofactors that are not traditionally considered 'pulmonary' in nature. We will review findings regarding some of these extrapulmonary cofactors, focusing on those most readily manipulated in the current clinical setting. RECENT FINDINGS: Recent studies have demonstrated that limiting fluid administration in the setting of acute lung injury might improve surrogate outcomes; that hypercapnea and induced hypothermia might protect against or attenuate acute lung injury; that corticosteroids can improve mechanics but not mortality in acute respiratory distress syndrome; a potential role for concomitant administration of colloid and diuretic in acute lung injury; and the potential benefits of inhaled beta agonists in acute lung injury. SUMMARY: There are a number of simple, low-cost, and rapidly deployable approaches to reducing the severity of acute lung injury that are not directly pulmonary in origin. These interventions could be rapidly implemented in any intensive care unit, once evidence for their efficacy and safety is adequate.