Endophthalmitis is a severe form of ocular inflammation. The source of pathogens in endogenous endophthalmitis is located inside the body, and infection spreads hematogenously. Although rare, endogenous endophthalmitis is a very serious condition, as this type of inflammation is very devastating for ocular tissues. Prognosis is very poor, and the patients are often in a serious general condition, so they require special care and an individual approach in the treatment process. Thanks to the knowledge of the risks associated with infections of individual tissues and organs as well as potential pathogens and the clinical picture, it is possible to make a correct diagnosis faster and implement the correct treatment. In the case of endogenous endophthalmitis, reaction time is absolutely crucial for prognosis. In this review, we focus primarily on the importance of the primary source of infection for the course of the disease and prognosis.