Lymphadenopathy is a common problem in children and adolescents. A wide variety of diseases and conditions may present as lymphadenopathy and an understanding of these conditions is essential to determine the most appropriate diagnostic work-up for each patient. A detailed history and physical examination with careful attention to the anatomical regions drained by the involved lymph node or mass often leads to the appropriate diagnosis. A majority of these children will prove to have a benign disorder; however, it is important for the pediatrician to have an appreciation for the malignant diseases or serious systemic illnesses that may initially present with lymphadenopathy, to ensure the timely diagnosis of a serious disease.