Immunotherapy with immune checkpoint inhibitors (ICIs) nowadays has indications for several solid tumors. The current targets for ICIs are CTLA-4, PD-1, and PD-L1 receptors. Despite the clinical advantages derived from ICIs, a variety of side effects are linked to overstimulation of the immune system. Among these, ICI-related colitis is one of the most common, with a disabling impact on the patient. Diarrhea, abdominal pain, abdominal distension, cramping, and hematochezia are the most common ICI enterocolitis presenting symptoms. The most frequently used grading system for assessment of the severity of ICI enterocolitis is called the Common Terminology Criteria for Adverse Events (CTCAE) grading. With regard to the histological picture, there is no specific feature; however, microscopic damage can be classified into five types: (1) acute active colitis, (2) chronic active colitis, (3) microscopic colitis-like, (4) graft-versus-host disease-like, and (5) other types. Supportive therapy (oral hydration, a bland diet without lactose or caffeine, and anti-diarrheal agents) is indicated in mild colitis. Symptomatic treatment alone or with loperamide, a low-fiber diet, and spasmolytics are recommended for low-grade diarrhea. In more severe cases, corticosteroid treatment is mandatory. In refractory cases, off-label use of biological therapies (infliximab or vedolizumab) was proposed.