Proctitis is an inflammation involving the anus and the distal part of the rectum, frequently diagnosed in the context of inflammatory bowel diseases (IBD). Nevertheless, when the standard therapy for IBD is ineffective, it becomes necessary for the clinician to review alternative etiologies, beginning from the broad chapter of infectious causes up to rare causes such as radiation, ischemia, diversion and traumatisms. While it is possible to find infectious proctitides caused by pathogens generally inducing extensive colitis, the growing incidence of both sexually transmitted infections and isolated proctitis reported in the recent years require a lot of attention. The risk appears to be higher in individuals participating in anal intercourse, especially men having sex with men (MSM) or subjects who use sex toys and participate to sex parties, dark rooms and so on. The commonest implicated pathogens are Neysseria gonorrhoeae, Chlamydia trachomatis, Herpes Simplex virus and Treponema pallidum. Herpes and Chlamydia infections mainly occur in HIV-positive MSM patients. Since symptoms and signs are common independently from etiology, performing a differential diagnosis based on clinical manifestations is complicated. Therefore, the diagnosis is supported by the combination of clinical history and physical examination and, secondly, by endoscopic, serologic and microbiologic findings. Particular emphasis should be given to simultaneous infections by multiple organisms. The involvement of experts in infectious diseases and in sexual health is crucial for the diagnostic and therapeutic management. The available therapies, empirically initiated or specific, in many cases are able to guarantee a good prognosis and to prevent relapses.