Nanoparticles and macromolecular carriers have been widely used to increase the efficacy of chemotherapeutics, largely through passive accumulation provided by the enhanced permeability and retention effect. Stimulus-responsive peptide and polymer vehicles can further enhance the efficacy of antitumor therapeutics compared with the administration of free drug by three mechanisms: increasing the overall accumulation within solid tumors; providing a homogeneous spatial distribution in tumor tissues; and increasing the intracellular localization of anticancer therapeutics. This article highlights recent developments in 'smart' - stimulus-responsive - peptide, polymer and lipid drug carriers designed to enhance the localization and efficacy of therapeutic payloads as compared with free drug.