Antibody Drug Conjugates (ADCs) are complex multi-domain biotherapeutics which combine, with the aid of a chemical linker, the tumor targeting properties of antibodies to the potent cytotoxicity of a selected small molecule (also called warhead or payload) to obtain novel pharmaceuticals for the treatment of cancer. ADCs are a rapidly growing class of pharmaceuticals with seven FDA-approved drugs already on the market and over eighty investigated at different stages of clinical development (1). The careful design of each of the ADC's building blocks allows to maximize anti-tumor efficacy while reducing the toxicity to healthy tissues. The preclinical characterization of these novel therapeutics requires the careful balance of the known requisites for small and biotechnology-derived molecules with a keen eye to the need of new effective treatments in the fight against cancer. From the analysis of official approval documents, available literature and current guidelines, this thesis will present the common features and peculiarities of the in vivo safety assessment of this emerging group of drugs. Moreover, this document will highlight the need for integrated and novel strategies for the preclinical evaluation of ADCs, stemming from their complex multi domain structure which sets them apart from both standard chemotherapy and antibody-based products.