Most therapeutic antibodies in the clinic today are based on fully humanised immunoglobulins. They have proven to be outstandingly effective, especially for the treatment of cancer, autoimmune and inflammatory diseases where the target is a single, well-defined and accessible molecule. Many diseases however are complex, involving multiple mediators or signalling pathways that could be targeted simultaneously to maximise clinical benefit. There is also a wealth of validated intracellular and CNS-based targets which are currently inaccessible to monoclonal antibody therapy. A spectrum of next generation immunotherapeutics is in development to address these issues and a number of them have also entered clinical trials.