Monoclonal antibodies, first introduced in cancer therapy and to prevent allograft rejection, represent new pharmacological tools for the treatment of autoimmune diseases. With the knowledge of immunological movements in autoimmunity, it is now possible to target each single step of the immune process, from the activation of T lymphocytes in lymph nodes to the formation of the immunological synapse, and to T cell differentiation and cytokine production. However, this approach is still not devoid of adverse effects. In fact, even if monoclonal antibodies exert selective immunomodulation by targeting only cells expressing a specific antigen, a widespread perturbation of the immune system is induced, leading to a predisposition for infections and infestations and to the occurrence of tumours.