Graves' disease (GD) is the leading cause of hyperthyroidism in children. However, compared to adults, GD in children is a rare condition. In a recent guideline issued by the European Thyroid Association, the diagnostic evaluation and treatment of pediatric GD is described extensively. In this article, we go beyond the guideline and describe the potential challenges of establishing the right etiology of thyrotoxicosis in children, illustrated by cases of thyroid hormone resistance, autonomous functioning thyroid nodules, and subacute thyroiditis with a thyrotoxic phase. In addition, we report therapeutic challenges in pediatric GD such as recurrent immunological flare-ups under antithyroid drug (ATD) treatment, innovative ways to improve ATD compliance and the role of definitive treatment in persistent complaints of malaise under ATD treatment.