For endosomal TLRs -TLR3 and TLR7-9, Talukdar et al. recently published a perspective paper regarding the structural evolution of their small-molecule agonists and antagonists. They concluded in detail information about structural features around binding sites of both types of modulators, and their evolution and provided information about the development of various chemotypes. Here we wanted to highlight a few studies not included in the above-mentioned publication.