During the last decade, new biotherapies have been developed for the treatment of systemic autoimmune diseases. These new approaches are based on a better understanding of the auto-immune response. Targets of these new treatments are the main steps of the immune response. These new treatments include: B lymphocytes inhibitors, inhibitors of the costimulation between antigen-presenting cells and T lymphocytes, T lymphocytes inhibitors, B and T lymphocytes inhibitors, modulators of the cytokine network, complement system inhibitors, and chemokines and integrins inhibitors. Advances in molecular biology, genetics and immunology have accelerated our understanding of auto-immune diseases, and allow identification of new targets. Development of new biotechnological tools with longer half-lives and increased affinity is an important next step. In spite of these exciting new perspectives, a systematic risk/benefit evaluation of these new treatments appears mandatory because immunity plays a key role in the control of infectious and tumor diseases. Further research is also needed to evaluate the cost/effectiveness ratio of these new therapies.