The development of gene silencing therapies for neurological diseases has placed great importance on the delivery of short interfering RNA (siRNA) to the central nervous system (CNS). However, delivery of siRNA to neurons, glia and brain capillary endothelial cells (BCECs) has not been well established. This editorial describes different approaches that are being used to efficiently deliver siRNA to the CNS via intravenous, intracerebroventricular, or intranasal administration.