The mechanisms by which immunoglobulin (Ig)G can modulate immunity have been investigated over the past few decades. In the past three years, some studies have demonstrated that IgG can play a pivotal role in mediating complex interactions that result in functional lymphocyte modulation during maturation in self or offspring primary lymphoid organs. This effect appears to be dependent on the IgG repertoire in the absence of the influence of antigens and the functionality of diverse cell populations, including B, αβT (CD4 T and CD8 T), invariant natural killer T and γδT cells, in mice and humans. Based on the literature, especially on findings resulting from the therapeutic use of purified IgG (intravenous Ig) and recent pieces of evidence obtained by my group, the “hooks without bait” theory is described here to guide the future development of therapies for specific immune regulation.