Antibody Drug Conjugates (ADCs) entered clinical trials in the mid 1990s to selectively deliver cytotoxic chemotherapy to cancer cells with the goal to increase the antitumor activity and decrease normal tissue toxicity. Over nearly 30 years of development the ADC platform has become established with now 11 approved agents and many more in the pipeline. This review is designed to highlight some of the problems and solutions encountered in clinical development as well as provide practical instruction to both clinical investigators on the efficient protocol design for ADCs and the lessons learned.