Indoleamine 2,3-dioxygenase 1 (IDO1) has received increasing attention due to its immunosuppressive function in connection with various diseases, including cancer. A recent increase in the understanding of IDO1 has significantly contributed to the discovery of numerous novel inhibitors, but the latest clinical outcomes raised questions and have indicated a future direction of IDO1 inhibition for therapeutic approaches. Herein, we present a comprehensive review of IDO1, discussing the latest advances in understanding the IDO1 structure and mechanism, an overview of recent IDO1 inhibitor discoveries and potential therapeutic applications to provide helpful information for medicinal chemists investigating IDO1 inhibitors.