INTRODUCTION: Fenfluramine (FFA) represents the latest therapeutic option approved for seizure management in Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) for patients aged ≥ 2 years. This article provides expert guidance for optimizing FFA therapy to support clinical decision-making in these populations. METHODS: A panel of Spanish experts specialized in developmental epileptic encephalopathies (DEEs) has developed practical recommendations for the clinical use of FFA, focusing on key aspects of FFA management: mechanism of action, pharmacokinetics including drug interactions, titration, efficacy, safety and tolerability, contraindications, and considerations for its broader application in DEEs. The methodology adopted in this project was an expert-opinion, evidence-based approach. RESULTS: The panel issued targeted recommendations, including a modified titration strategy slower than the product guidelines, adjusted for possible antiseizure concomitant medications, and management of other concomitant treatments. Key efficacy indicators, such as reductions in seizure frequency and severity of the most disabling seizures, were emphasized as core measures for treatment evaluation. Periodic assessments of non-seizure outcomes and daily life activities are recommended during follow-up to comprehensively capture treatment outcomes. The panel noted that their clinical observations align with positive findings from clinical trials, suggesting a potential role for FFA in other DEEs, tailored to individual electroclinical and etiological profiles. CONCLUSION: This article presents expert practical recommendations for the management and treatment optimization of FFA in patients with DEEs, supporting clinicians in achieving improved patient outcomes.