Hemophagocytic lymphohistiocytosis (HLH) has been reported rarely with BRAF/MEK inhibitor combinations, including dabrafenib/trametinib. Postmarketing pharmacovigilance analyses evaluating outcomes associated with dabrafenib/trametinib-induced HLH are also lacking. Herein, we report a case of dabrafenib/trametinib-induced HLH in a patient with metastatic melanoma. Recovery of HLH-related symptoms was observed following drug discontinuation, supportive care, and corticosteroids. We also conducted a pharmacovigilance analysis of the USA Food and Drug Administration Adverse Event Reporting System (FAERS) to describe postmarketing cases of HLH with dabrafenib/trametinib exposure. There were 50 reports of HLH with dabrafenib/trametinib in FAERS. Most cases occurred in the setting of melanoma ( n = 39; 78%) and most were reported in Europe ( n = 39; 74%). Hospitalization was the most common outcome ( n = 39; 78%) of this adverse event per FAERS. HLH is a rare complication of dabrafenib/trametinib, and clinicians should be aware and monitor for signs of this potentially serious and life-threatening adverse event.