Aptamers are single-stranded DNA or RNA oligonucleotides that assume specific 3D structures and bind to target molecules with high affinity. The unique specificity of aptamers has made them attractive agents for targeted cancer therapy. Aptamers have been developed against a variety of cancer targets, including extracellular ligands and cell surface proteins. In addition, aptamers have been incorporated into novel constructs involving siRNAs, chemotherapeutic agents, cell toxins and nanoparticles, in which they function as delivery agents for therapeutic cargo. In this article, we review recent developments in the use of aptamers for targeted cancer therapy, particularly focusing on novel applications of aptamers targeting the cell surface.