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ABSTRACT: The respiratory system, as well as the skin, are organs in direct contact with the environment and it they represent possible doors for the entrance of therapeutic agents into the body. Because of the increasing incidence of pulmonary diseases with high mortality and morbidity, pulmonary drug delivery is emerging as a non-invasive and attractive approach for the treatment of several pathologies. It must be pointed out that the development of drug delivery systems for pulmonary application requires a detailed knowledge of the lung, both in its healthy and disease state. Among the various drug delivery systems considered for pulmonary application, nanocarriers show several advantages over other conventional approaches for the treatment of respiratory diseases, for example prolonged drug release and cell-specific targeted drug delivery. Nano-size drug carriers can incorporate various therapeutics (e.g., poorly water soluble drugs, macromolecules) and show interesting features as drug delivery systems to the lung, such as: controlled release, protection from metabolism and degradation, decreased drug toxicity and targeting capabilities. Since gene therapy (e.g. small interfering RNA, siRNA) is currently being developed for a wide range of acute and chronic lung diseases, including CF, cancer and asthma, the use of nanocarriers for lung release/targeting represents a promising application of such nano-sized structures. Despite the many promising proof of concepts of various delivery technologies reported in this review, further efforts are needed to ensure the safety of long-term in vivo applications and the development of scale up from laboratory to industry in order to reach, together with safety, large - scale production at affordable costs of innovative lung delivery technologies.