Abstract Background Hyperthermic isolated limb perfusion (HILP) is used for patients with intractable or extensive in-transit metastatic melanoma of the limb to deliver high concentrations of cytotoxic agents to the affected limb and offers a treatment option in a disease stage with a poor prognosis when no treatment is given. Methods In a retrospective chart review of 17 cases, we studied the anesthetic and hemodynamic changes during HILP and its management. Results HILP was well tolerated except in one case that is described herein. We present summary data of all cases undergoing upper and lower limb perfusion, discuss our current clinical practice of preoperative, perioperative and intraoperative patient care including the management of HILP circuit. Conclusion HILP is a challenging procedure, and requires a team effort including the surgical team, anesthesia care providers, perfusionists and nurses. Intraoperatively, invasive hemodynamic and metabolic monitoring is indispensable to manage significant hemodynamic and metabolic changes due to fluid shifts and release of cytokines.