RNA drugs are an emerging class of therapeutics that address diseases at the genomic and/or transcriptomic level. However, their widespread clinical translation is hampered by many extra-and intracellular barriers, including undesired immune activation and ineffective delivery across cell membranes. To broaden the therapeutic scope of RNA, a great interest exists in their delivery to extrahepatic tissues, with the lung being an attractive target organ. For many respiratory pathologies an unmet therapeutic need exists. However, in spite of many advantages of RNA inhalation therapy, to date no innovative RNA nanomedicines are available for application in the lung. A major objective is therefore to develop key enabling RNA delivery carriers for pulmonary application. Moreover, ample attention is given to the optimization of the nanocarriers to cross the various extra-and intracellular barriers in the lung tissue and to maintain optimal performance following inhalation therapy approaches.