Regulatory autoantibodies against G protein-coupled receptors as well as against growth factors and growths factor receptors are an elegant answer to these questions. These antibodies are present in healthy individuals and form an interacting network between various pathways. Specific alterations of this ab network are found between male and female person, in older versus young people, but much more pronounced in autoimmune and so called non-autoimmune diseases such as Alzheimer Disease or Cancer. Those antibodies also could explain syndroms such as fibromyalgia or chronic fatigue syndrome, diseases with a high burden on quality of life. Currently, we are deciphering the role of these antibodies in diseases and Graves’ disease is one of the prominent diseases for antibody-effects. We are working on systemic autoimmune diseases providing an ideal field to understand effects of the antibodies due to their genetic predisposition for a disturbed immune regulation, the heterogeneity of clinical symptoms, complex interactions with the environment, as well as the presence of co-morbidities. The ultimative goal is to identify better therapies, which will be discussed. However, addressing the antibody-receptor interactions and respecting these antibodies as novel ligands modulating receptor functions independent and different from the natural ligands is one of the most challenges in the future.