RNA interference is a post-transcriptional gene-silencing pathway induced by double-stranded small interfering RNA (siRNA). The potential use of siRNA as a therapeutic agent has attracted great attention as a novel approach to the treatment of several intractable diseases. Despite the rapid progress in the therapeutic use of siRNA, systemic application is still controversial due to the limitations of siRNA, such as low enzymatic tolerability, cellular internalization and body distribution after systemic administration. This review describes the recent progress and strategies of siRNA delivery systems based on polyion complexes. Numerous siRNA-containing polyion complex systems bound together through electrostatic interactions between the negatively charged siRNA and positively charged components, including synthetic polymers, biopolymers and nanoparticles, have been developed for the therapeutic application of siRNA. Additionally, stimulus-sensitive smart siRNA carrier systems, including bioreducible polycations and hydrophilic polymer-siRNA conjugates, have been developed to enhance the gene-silencing efficacy of siRNAs.