RNA interference (RNAi) has been emerged as an effective method to silence a particular gene utilizing a sequence‐specific mechanism for gene regulation. It induces target mRNA degradation leading to a lower illness‐inducing gene product. RNAi represent a conserved mechanism. Novel concept of highly specific silencing of genes was revolutionized by the introduction of short interfering RNA (siRNA).This helped to overcome the drawbacks of RNAi and proved out to be a safer and efficient method than its counterpart finding its way into the pharmaceutical industry. Clinical trials enhanced the possibility of siRNA delivery and yielded promising results for the treatment of a wide range of illnesses but mainly for intractable diseases like cancer, inflammatory diseases, and genetic disorders. siRNA delivery methods were instrumental in developing it as a therapeutic, of which lipid encapsulation crept its way, to be a better in vivo delivery mechanism as it could be formulated effectively, being biodegradable, and has a lower toxicity level. However, the therapeutic potential of siRNA remains hampered due to a lack of a viable delivery method, a lower accuracy in tissue specificityand cytotoxicity. Hence the therapeutic usage of the method is in its budding stage. This review re‐examines the principle of siRNA, challenges in its delivery, and some recent advancesto overcome the obstacles in order to improve siRNA delivery.