The potential use of many promising novel drugs is limited by their inability to specifically reach their site of action after intravenous administration, without secondary effects on healthy tissues. In order to remediate this problem, the protein transferrin (Tf) has been extensively studied as a targeting molecule for the transport of drug and gene delivery systems to the brain and cancer cells. A wide range of delivery approaches have been developed to target the Tf receptor and they have already improved the specific delivery of Tf-bearing therapeutic agents to their site of action. This review provides a summary of the numerous delivery strategies used to target the Tf receptor and focuses on recent therapeutic advances.