Most current therapeutic approaches focus on targeting a protein or its function after it has been translated. A therapeutic approach that is gaining interest is altering the mRNA that encodes for a disease associated protein and preventing the protein from being produced. There are two major therapeutic methods to alter mRNA levels, antisense and RNA interference (RNAi). Currently, antisense is the more developed technology and has been extensively used in vivo. As this review will mostly focus on in vivo studies, animal models or humans, it will concentrate on antisense. The lung is an attractive target for this technology as the drug can be introduced to the organ with limited systemic involvement. Inflammatory diseases of the lung, such as allergy or asthma, are potential areas in which antisense technology could be beneficial. There are many mRNA targets being investigated for treatment in inflammatory lung disease that include signaling molecules as well as receptors. Also, antisense is being investigated for treatment of lung cancers. In lung cancer, some oncogenic genes may be unique to the tumor and can be specifically targeted without affecting other cellular processes. Thus, antisense and RNAi potentially provide an alternative to current therapy for treatment of pulmonary disorders.