The clinical potential of siRNAs for silencing genes critical to disease progression is clear, but a fail-proof method for delivering siRNAs to the cytoplasm of diseased tissues or cells has yet to be identified. A variety of delivery approaches have been explored to directly or indirectly couple siRNAs to delivery vehicles. This review explores the use of synthetic single-stranded DNA and RNA aptamers as a means to deliver siRNAs, shRNAs and antisense oligonucleotides for therapeutic intervention. Topics covered include: the advantages and challenges of using aptamers as delivery tools; current aptamer-mediated siRNA delivery platforms for the treatment of cancer and HIV; and emerging methodologies for the identification of aptamers capable of internalizing into target cell types.