Antibodies have emerged as significant agents for the treatment of a number of diseases including cancer and autoimmunity. However, most of the antibodies currently used in clinical practice were developed from humanized or chimeric molecules based on mouse monoclonal antibodies. Recent advances in antibody selection and engineering techniques have led to the development of antibodies specific for highly conserved targets, the creation of novel antibody-based structures, significant improvements in affinity for target antigens, enhanced ability to engage immune effector functions, and the creation of fusion proteins with direct cytotoxic properties. This review provides an overview of the techniques that we expect will have the greatest impact on the field of antibody engineering.