Monoclonal antibodies are at the forefront of novel therapeutic strategies for cancer and have made a positive impact on the clinical management of several malignancies. Success in the clinic was originally demonstrated in hematological cancers with the regulatory approval of the anti-CD20 monoclonal antibody rituximab for the treatment of non-Hodgkin’s lymphoma in 1997 and subsequently with the anti-HER2 trastuzumab for the treatment of breast cancer in 1998. Early research and development efforts concentrated on the design of antibodies that selectively target cancer cells or tumor-associated vasculature. In the last decade, two further antibody classes have emerged: checkpoint inhibitors capable of targeting checkpoint molecules on immune cells to activate immune responses against tumors and antibody-drug conjugates, comprising monoclonal antibodies conjugated to toxic payloads to deliver these specifically to tumor cells. A clearer understanding of an antibody’s functional profile may pave the way for identification of the most highly efficacious agents for specific patient groups.