Congenital lipodystrophy is an uncommon autosomal recessive disorder that occurs mainly in females and is characterized by loss of subcutaneous fat, insulin-dependent diabetes mellitus, and masculinization due to defective metabolism of fat. Acquired lipodystrophy is now most commonly encountered in patients infected with HIV who take protease inhibitors. We present an illustrative case of lipodystrophy and review the presenting signs allowing for an accurate clinical diagnosis.