Isotretinoin has been widely prescribed for the management of moderate to severe acne vulgaris worldwide. It has been associated with different sleep disorders, mainly sleep apnea and hypersomnia. To our knowledge, only one study has found an association between isotretinoin use and insomnia. In addition, psychiatric disorders, such as psychosis and depression, have been linked to the use of isotretinoin previously. Here, we present a case of a 21-year-old male patient with severe acne vulgaris that underwent a therapeutic course of isotretinoin. During the course of treatment, he developed severe insomnia and depression. By reducing the daily dose, his insomnia was treated, as well as his depression. This case led to the conclusion that isotretinoin is associated with severe insomnia, and the severity of insomnia is dose-dependent.