Molecular therapy with small interfering ribonucleic acid (siRNA therapeutics) has demonstrated enormous clinical potential against a variety of fatal pathologies caused by atypical gene overexpression or genetic mutation. Significant progress has been made in siRNA-based therapeutics in an astonishingly short period of time. It is extremely difficult to explore the full potential of such gene-based therapeutic approaches without ensuring the safe and effective delivery of SiRNA to the target sites. Due to various limitations associated with viral-based approaches and limited or slow progress in non-viral counterpart development, the current methods of siRNA delivery materials and their diversity remain limited. This chapter elaborates on the importance of siRNA in disease management, as well as the evolution of nanoparticle systems in the efficient transfer of siRNA to target sites, which leads the technology to clinical application. The classification of siRNA nanocarriers and the rationale underlying the application of these nanocarrier systems that have been studied so far are specifically discussed.