A key concept in medicine is that rational therapy rests on accurate diagnosis; quite simply, therapy that is not tuned to the cause of the disease will not cure the patient. I do not mean to say that effective treatments cannot emerge from faulty diagnoses. In truth, much of our therapeutic ensemble is composed of drugs developed as a result of chance observation, random, screening, intuition, or pre-scientific tradition. Nevertheless, the way to effective therapy is best paved by understanding. Effects are inherent in their causes; so if we want to cure autoimmune diseases using the scientific method, we are obliged to inquire into their causes. By reducing the discordant complexity of the disease to the single cause that underlies it, we can hope to learn the most efficient way to manipulate the disease process. How do we identify a cause when we see one? Quite simply, a single cause is that which is both necessary and sufficient to produce the effect. Here, I explore the general paradigm of autoimmune causality, using multiple sclerosis as a specific example.