RNA interference (RNAi) is a post-transcriptional mechanism of gene silencing that involves the generation of small interfering RNA (siRNA), micro RNA (miRNA), short hairpin RNA (shRNA) molecules from double stranded RNA (dsRNA) that are capable of binding to host mRNA molecules and inhibiting their translation and enhancing the degradation of the mRNA, so that leads to inhibition of gene expression of defective gene by suppression of the protein synthesis. This robust silencing effect of RNAi makes it a valuable research tool both in cell culture and in living organisms, in various diseases like cancer, metabolic syndrome, viral disease (HIV-1, Hepatitis B), neural and neuromuscular diseases (Muscular dystrophy, Spinal muscular atrophy, Alzheimer disease), Poly(Q), Parkinson, Asthma and Diabetes. Although introducing siRNA into cells in vivo remains a significant obstacle, as it is imperative for siRNA to reach the cytoplasm of the targeted cells because naked RNAs cannot penetrate cellular lipid membranes by themselves to become effective and induce silencing. So to overcome this challenges of delivery viral vectors like adenovirus and lentivirus and nonviral vectors like naked RNA, lipid based delivery vectors, cell penetrating peptides, polymer, inorganic molecules, chemical conjugates. Key words: dsRNA, siRNA, miRNA, shRNA