The endoplasmic reticulum (ER) is the primary site for the folding of proteins destined for the membranous compartment and the extracellular space. This elaborate function is coordinated by the unfolded protein response (UPR), a stress-activated cellular program that governs proteostasis. In multicellular organisms, cells have adopted specialized functions, which required functional adaptations of the ER and its UPR. Recently, it has become clear that in immune cells, the UPR has acquired functions that stretch far beyond its original scope. In this review, we will discuss the role of the UPR in the immune system and highlight the plasticity of this signaling cascade throughout immune cell development .