Compliance with prescribed medication is an important but complex issue which is incompletely understood, Depression is also a factor that can lead to noncompliance. A 30-year-old lady was seen in the outpatient clinic with complaints of palpitations and tremor. Her medical history revealed a subtotal thyroidectomy for multinodular goiter five years earlier. During a period of depression, she stopped taking levothyroxine for 45 days. Discontinuation of therapy worsened her depression. At her visit, the dosage of levothyroxine was increased, and the symptoms of depression improved. However, increasing the dosage of thyroid supplement resulted in a hyperthyroid state. The role of depression on noncompliance is also discussed.