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INTRODUCTION: Lipedema is a chronic and progressive disease that predominantly affects women, characterized by a disproportionate increase in subcutaneous adipose tissue (AT), particularly in the lower limbs. It is associated with significant physical disability, chronic pain, thromboembolism, and psychosocial distress. Despite its profound impact on women's health and quality of life, lipedema remains underrecognized and insufficiently studied, with an estimated prevalence of approximately 10% among women worldwide. Although the exact etiology of lipedema remains unclear, emerging evidence suggests a multifactorial origin involving genetic predisposition, hormonal influences, and vascular dysfunction-all contributing to its development and progression. Current therapeutic options provide only partial symptom relief and remain noncurative, highlighting the urgent need for expanded research and improved management strategies. METHODS: A systematic review was conducted to assess the current understanding of lipedema pathophysiology and current treatment options. Research articles were sourced from PubMed, Web of Science, ScienceDirect, and Scopus databases. Over 100 studies were incorporated. RESULTS: This review provides a comprehensive overview of lipedema, encompassing its clinical features, pathophysiological mechanisms, diagnostic challenges, and current treatment modalities. Additionally, the review discusses whether the molecular and metabolic differences between abdominal and femoral AT depots mirror those observed in classical obesity. CONCLUSIONS: Multidisciplinary, research-informed care is essential for managing lipedema, combining conservative therapies, tailored exercise, and liposuction for advanced cases. More research to better understand the underlying pathophysiology is critical to developing targeted treatments, improving diagnostic accuracy, and informing standardized, evidence-based care.