This article will review recent developments in the field of gene silencing as a therapy for respiratory and related inflammatory and immunologic diseases. The respiratory epithelium offers an attractive target for therapies derived from nucleic acids since the respiratory epithelium contains endogenous lipids that can facilitate uptake of polar nucleic acids and related compounds. Both RNAi (RNA Interference) in which a messenger RNA (mRNA) is targeted by an endogenous enzyme complex termed RISC (RNA Interference Silencing Complex, also previously termed RNA Induced Silencing Complex in earlier references) and also gene silencing using EGS (External Guide Sequences) in which a messenger RNA (mRNA) is targeted by an endogenous RNA enzyme termed RNase P are summarized including selected patents. The strengths and limitations of these technologies such as problems of delivery to specific tissues and potential for non-specific inflammatory response and off-targeting are compared. The possibility of therapy designed exploit synergies between both RISC and RNAse P and therapeutic benefits of inhibiting either or both pathways are also considered.