Abstract : Objective To perform a systematic review of the literature on the effectiveness of inhaled nitric oxide in the treatment of acute chest syndrome in patients with sickle cell disease and to explore the genetic implications of this review. Methods Electronic databases were searched from their initiation to 2007. Additional searches were carried out of abstracts of conference proceedings. These comprehensive searches yielded 9 citations all of them are randomized controlled trials. None of the trials examined the use of inhaled nitric oxide in acute chest syndrome. Results No relevant trials matching the inclusion criteria of this systematic review were identified. This reflects the lack of clinical trials on patients with acute chest syndrome despite the high prevalence of the disease. A descriptive summary was presented and a new therapeutic modality in the form gene therapy is proposed. Conclusion Although no trials were identified to answer the research question in this review, there is evidence that inhaled nitric oxide may be effective in the treatment of acute chest syndrome, but to support this, well-designed randomised controlled trials are needed. Nitric oxide synthase gene transfer may hold promise as a future therapeutic strategy for acute chest syndrome.