Over the last decade, considerable effort has been put in the implementation of RNA interference (RNAi) as a treatment for various disorders. As RNAi occurs in the cytoplasm of cells, it is imperative that RNAi mediators such as small interfering RNA (siRNA) cross several extracellular and intracellular barriers to reach this site of action. Among the extensive range of proposed delivery systems for siRNA, matrix systems possess interesting properties to promote the delivery of siRNA to a target tissue. In this review, a number of recently developed matrix and hybrid systems for siRNA delivery are discussed.