Duodenal perforation is a rare occurrence and is associated with high mortality, which rises to 30–50% in cases that involve associated peritonitis. The most frequent etiologies include peptic ulcer, post-operative fistula, endoscopic perforation, and trauma. The challenge in managing this pathology lies in the fact that resection with anastomosis is often unfeasible, and the creation of a stoma is not possible. Management must be tailored on a case-by-case basis that always involves medical measures, often endoscopic interventions, and sometimes surgery. Indeed, the surgical option is feasible in selected patients who are diagnosed early and present without complications. Surgical procedures are classified into two categories: preferably, reconstructive procedures—where resection of the perforation and restoration of digestive continuity is possible, provided that local and hemodynamic conditions are favorable; conversely, a duodenojejunal diversion procedure—in which the perforation is left in situ while enteric secretions are diverted—is the preferred approach when conditions are unfavorable. When local conditions are unfavorable, or there is hemodynamic instability, duodenostomy drainage is the preferred option. This technique involves directing duodenal secretions toward the skin, thereby inducing the formation of a fibrotic fistulous tract with eventual wound healing. The management of duodenal perforation is a lengthy and challenging process.