Hypersensitivity reactions of the immune system have been broadly categorized into the atopic and autoimmune depending on whether the antigen triggering the reaction is endogenous (or self) or exogenous, the types of cellular and humoral components involved, and the clinical symptoms. Research into the pathophysiology of the resultant disease states has focused on a dichotomy between Th1 and Th2 T helper lymphocytes thought to govern autoimmune and atopic disease, respectively. Recent discoveries, however, have served to dispute this paradigm and have provided additional insight into the roles of Th17 cells, B-lymphocytes and T regulatory cells as well as the considerable communication and commonalities between the complex signaling pathways. Furthermore, clinical studies have served to challenge the idea that the presence of atopy and autoimmunity are mutually exclusive states. Finally, application of recent approaches to treatment-biologic targeted therapy in autoimmunity and induction of immune tolerance in atopic disease--to both disease states have shown mixed but promising results.