Purpose of reviewOutcomes after lung transplantation are poor, largely because of chronic rejection. Increasing immunosuppression to control rejection frequently results in toxicity and opportunistic infection. Aerosol cyclosporine was developed with the rationale that high concentrations of cyclosporine delivered to the lung by aerosol inhalation would result in improved rejection control with limited systemic cyclosporine exposure. Here we describe the developmental history of inhaled cyclosporine and review our ongoing trials to evaluate its use as a promising new therapy for lung transplant recipients.Recent findingsAfter demonstrating safety and efficacy in animal transplant models, clinical trials using rescue open-label, inhaled cyclosporine in human lung transplant recipients with bronchiolitis obliterans and refractory acute rejection demonstrated improvement in pulmonary function and survival. A therapeutic response was dependent on the absolute quantity of cyclosporine measured within the allograft. In 1998, a randomized, placebo-controlled trial was initiated using inhaled cyclosporine in addition to oral immunosuppression. An interim analysis showed that lung function was superior in patients randomized to inhaled cyclosporine who deposited at least 5 mg in the allograft compared with placebo aerosol.SummaryInhaled cyclosporine was safe and improved outcomes in lung transplant recipients with refractory acute and chronic rejection. An interim analysis of a placebo-controlled, randomized trial showed that inhaled cyclosporine improves lung function compared with placebo aerosol. Inhaled cyclosporine should become a standard treatment after lung transplantation if a final analysis of this recently completed trial demonstrates a reduction in the incidence of chronic rejection.