A decade ago, the discovery of the high-affinity receptor for IgE (FcepsilonRI) on epidermal Langerhans cells documented the end of the dogma that FcepsilonRI is only expressed on effector cells of anaphylaxis. Since then, the functional significance of this receptor on antigen-presenting cells (APCs) has been an area of intense research work. Scientists have focused on a better understanding of the molecular structure, regulation, and role of FcepsilonRI on APCs in the human immune system. Insights into the cellular events linked to the activation of APCs on ligation of FcepsilonRI by IgE and allergens might provide the basis for new aspects in the pathophysiology of allergic diseases and the design of future diagnostic and therapeutic strategies. This review is dedicated to the 10th anniversary of the discovery of FcepsilonRI on APCs and describes the numerous areas of research in this field.