Graves’ disease (GD), the leading cause of persistent hyperthyroidism in adults, is an autoimmune disease that primarily affects the thyroid gland and also may affect multiple other organs, including the heart, eyes, and skin. Among the currently available treatment modalities for GD are antithyroid drugs (ATDs), radioiodine ablation (RIA), and thyroidectomy. However, these treatment modalities have certain limitations. For example, ATDs are associated with a high risk of hyperthyroidism relapse, and definitive therapy, either RIA or thyroidectomy, is associated with permanent hypothyroidism, requiring lifelong thyroid hormone replacement therapy. So far, no consensus has been reached regarding the optimal treatment modality for GD. Currently, ATDs are regarded as the most preferred first-line treatment worldwide. According to the traditional standard of care, patients with GD should be treated with ATDs for 12 to 18 months. However, the relapse rate following ATD therapy is usually high (approximately 50%), and many patients require additional treatment. Therefore, whether long-term ATD (LTATD) treatment (60 months or more), relative to standard treatment for 12 to 18 months, reduces the frequency of relapse in patients with GD remains unclear. In addition, the predictive factors of remission or relapse for GD remain a matter of debate. The current paper summarizes the evidence available on LTATD treatment, focusing both on its efficacy and safety in patients with GD and on its effect on the remission rate of hyperthyroidism. The paper also presents a review of the current knowledge available regarding the predictors of GD relapse following ATD treatment.