Endophthalmitis is a frequent blinding complication of globe-penetrating injury and ocular surgery. The outcome of this intraocular infection depends both on the organism involved and management of the ensuing inflammation. The role of various toxins and bacterial factors in the pathogenesis of this infection is beginning to be delineated, but appears to be organism specific. Because of the immune-privileged environment of the eye, principles important in the resolution of infection at extraocular sites cannot be extrapolated to understanding the host-parasite dynamics in eye infection. Moreover, some factors that suppress the intraocular immune environment appear to have unexpected roles in activating phagocytic cells of the innate immune system in response to the presence of bacteria. Therefore, considerable additional information characterizing the precise role of bacterial and host factors in the pathogenesis of endophthalmitis will be required in order to develop new therapies to improve the outcome of this often blinding infection.