Lipedema is a debilitating disease caused by abnormal and excessive accumulation of subcutaneous fat, primarily affecting the lower and upper limbs. It is primarily affecting women and is influenced by sex hormones. The global prevalence of lipedema is estimated to be 1–9/100,000. However, it can be misdiagnosed and confused with other diseases like obesity and lymphedema. Lipedema is generally limited to the limbs and may be normal, while obesity has generalized fat accumulation with a high body mass index (BMI). Lymphedema is bilateral and associated with pain and bruising, while lipedema can be unilateral and characterized by a positive Stemmer sign. Dieting cannot effectively improve lipedema, but it can reduce obesity associated with it. Lipedema can be an independent disease or part of a syndrome, with diagnosis based on medical history, physical examination, blood tests, and imaging techniques.