Cytotoxic drugs, which are commonly used for the pharmacotherapy of many forms of cancer, often cause substantial toxicity to the patient without being able to induce long-lasting remissions. Ligands specific to accessible tumor-associated targets, capable of selective localization at the neoplastic site, may facilitate the preferential delivery of anti-cancer drugs, boosting activity and helping spare normal organs. In this article, we present a critical analysis of the limitation of conventional anti-cancer drugs and we contrast monoclonal antibodies and small organic ligands, as vehicles for pharmacodelivery applications.