Publisher Summary This chapter discusses the past and futures approaches for immunologic therapies in multiple sclerosis (MS). It also explores why the past therapeutic approaches failed and what these failures could mean to the concepts of pathogenesis and trial design. Future therapeutic approaches are also discussed and the most important examples are listed and named including pathogenetically oriented immune therapies, immunosuppressants and immunomodulators, novel immunomodulatory agents, and autologous stem cell transplantation. The examples from the past as well as the most important samples from future approaches for therapy are tabulated. Past approaches discussed are: modification of the cytokine pattern, chemotaxis, immunosuppressants, remyelination, and antigen-derived therapies such as altered peptide ligands. Despite the tremendous progress in MS therapy over the last years, the number of therapeutic strategies that failed to show benefit for MS patients, demonstrated a critical risk-benefit ratio, and raised controversies in terms of their assumed efficacy or practicability is considerable. The most important substances under development are summarized and highlight the possible sites of drug action. Major groupings of agents or strategies described are: (1) pathogenetically oriented immune therapies, (2) immunosuppressants and immunomodulators, and (3) autologous stem cell transplantation. Nevertheless, meaningful preclinical studies in animal models are indispensable to develop and verify rational therapeutic concepts in the future.