Small interfering RNAs (siRNA) are one of the most recent additions used to silence gene expression. At present, siRNA is the most extensively used gene-silencing technique over other nucleic-acid based approaches to treat diseases including cancer, hepatitis, respiratory disease, cardiovascular diseases, neuronal disease and autoimmune disease. However, systemic delivery of siRNA remains to be the biggest challenge to be overcome. Various strategies have been developed to deliver siRNA efficiently into target cell such as chemical modification of siRNA, physical strategies, viral and non viral-vectors mediated delivery. Among all the approaches non viral vectors including lipoplexes, polyplexes and inorganic nanoparticles were found to be most successful which have been reviewed in this article. Further therapeutic applications of RNAi have also been briefly reviewed.