Autoimmune disorders have been on a steep rise in the industrialized countries over the past several decades and while research has been starting to develop a detailed understanding of pathophysiology and many of the underlying mechanisms, any meaningful incorporation of this information into clinical medicine has been painfully slow. Concepts of molecular mimicry, the hygiene hypothesis, intestinal hyper-permeability (leaky gut syndrome) and aggressive use of predictive antibody testing are explored in this article with examples given on how emerging information on these phenomena may aid the clinician in a new, more proactive, approach to management of these conditions.