The removal of immune complexes in humans depends primarily on the complement receptor pathway and to a lesser degree the FcγR. Among the FcγRs, it has been widely believed that immune complex removal only occurs by phagocytosis/endocytosis of activating‐type FcγR. Surprisingly, the inhibitory FcγRIIb, which lacks intrinsic activating function, plays a major role in clearance, and rapidly “sweeps” away small complexes from the circulation (Figure 1d).48, 49 A major tissue involved in the clearance is likely to be the LSEC, where FcγRIIb is expressed abundantly in mice and humans. This role is potentially important in resistance to viruses and toxins but may also be key to optimal performance of therapeutic IgG mAbs whose primary MOA is believed to be only neutralization of soluble macromolecules, for example, cytokines or IgE.