Antibody-drug conjugates (ADCs) are a therapeutic modality that enables the targeted delivery of highly potent cytotoxic payloads to tumors. This chapter describes the components of the ADCs and discusses the medicinal chemistry principles that guide the design of this class of therapeutics. A description of main classes of drugs and the linkers used to attach to monoclonal antibodies with an emphasis on the design, historical development, and linking strategies is presented. Clinical use of the approved ADCs for the treatment of cancer is briefly described.