The generation of long-lived plasma cells and memory B cells producing high-affinity antibodies depends on the maturation of B cell responses in germinal centers. These processes are essential for long-lasting antibody-mediated protection against infections. IgE antibodies are important for defense against parasites and toxins and can also mediate anti-tumor immunity. However, high-affinity IgE is also the main culprit responsible for the manifestations of allergic disease, including life-threatening anaphylaxis . Thus, generation of high-affinity IgE must be tightly regulated. Recent studies of IgE B cell biology have unveiled two mechanisms that limit high-affinity IgE memory responses: First, B cells that have recently switched to IgE production are programmed to rapidly differentiate into plasma cells, and second, IgE germinal center cells are transient and highly apoptotic. Opposing these processes, we now know that germinal center-derived IgG B cells can switch to IgE production, effectively becoming IgE-producing plasma cells. In this chapter, we will discuss the unique molecular and cellular pathways involved in the generation of IgE antibodies.