This chapter reviews the development of antibody–drug conjugates (ADCs) since the initiation of the concept of “magic bullet” by Paul Ehrlich more than 100 years ago. The main focus of the chapter is on the early exploratory approaches that were taken to prove the feasibility of antibody-mediated drug delivery. The progress of ADC development correlated closely with the advances of the knowledge and technology in immunology, conjugation chemistry, molecular biology, and cell biology. Results from these diverse studies in different scientific disciplines during the past half century have slowly established ADCs as a new category of biotherapeutics in cancer therapy. Currently, there are more than 10 ADCs that have been approved by the FDA for the treatment of various types of cancer.