Recurrent/metastatic head and neck cancers remain incurable diseases despite the development of molecularly targeted therapies and immunotherapies. The antibody-drug conjugates (ADCs) are emerging as a novel therapeutic class which integrate the precision of monoclonal antibodies with a cytotoxic drug, referred to as the payload, through a chemical linker, with the aim of selectively delivering this highly toxic payload directly to the cancer cells and, thereby, enhancing the therapeutic index. Various ADCs have been explored and validated across various solid malignancies: the first FDA approval in 2013 was for breast cancer with ado-trastuzumab emtansine, followed by trastuzumab deruxtecan in 2019 and sacituzumab govitecan in 2020. By 2020 additional approvals have been extended for urological and cervical cancers. Currently, over 100 ADCs candidates are in different stages of clinical research. In early phase trials for advanced head and neck cancers, several ADCs with a variety of targets are being investigated. Here, we provide an overview of ADCs structure and biology, outlining the results of the most recent clinical trials with ADCs in patients with recurrent/metastatic head and neck cancers including salivary gland cancers and nasopharyngeal cancer. These trials have shown acceptable toxicity and encouraging efficacy, particularly those targeting the epidermal growth factor receptor and the tissue factor.