Bacillus endophthalmitis is one of the most devastating intraocular infections, frequently resulting in significant vision loss, if not loss of the eye itself, in only a few days. This review summarizes recent research focused on characterizing the interactions between Bacillus and the host response during endophthalmitis. Analyses of the contribution of Bacillus toxins and cell wall components, and the behavior of the organism during progressive disease are discussed. A better understanding of the host/pathogen interactions occurring during endophthalmitis is critical for the development of novel therapeutic agents designed to impede the progression of infection and protect vision.