With the advent of targeted therapies came a new paradigm for cancer treatment. The specific interaction between ligands and surface receptors has been exploited to increase the specific accumulation of drugs or drug-loaded nanoparticles inside cancer cells, thus improving overall efficacy and reducing side effects. Being overexpressed in several solid tumors, the human epidermal growth factor receptor 2 (HER2) is a valuable target receptor in cancer therapy. Apart from therapeutic applications, a monoclonal antibody against HER2, called trastuzumab, has found widespread use as a targeting ligand. The surface of trastuzumab enriched with reactive functional groups provides opportunities for conjugation with drug molecules and different types of nanoparticles, yielding a myriad of antibody-drug conjugates and antibody-conjugated nanoparticles, respectively. This chapter focuses on the use of trastuzumab as the targeting moiety in targeted cancer therapies. After providing an overview of trastuzumab and the trastuzumab-drug conjugates developed so far, the authors highlight studies using trastuzumab-conjugated nanoparticles directed to HER2-positive breast cancer, HER2-positive gastric and esophageal cancers, and other HER2-positive cancers. Some examples of trastuzumab fragment-conjugated nanoparticles are also discussed.