We report on 2 cases of the effect of modafinil on the self-esteem of patients with spinal cord injury (SCI). The first patient was a 33-year-old man with history of polysubstance abuse and a C6 American Spinal Injury Association (ASIA) grade A injury, who presented for follow-up to the outpatient rehabilitation clinic for depression, decreased motivation, and lowered self-esteem. The patient had tried a selective serotonin reuptake inhibitor (SSRI) without success, and reported increasing social and legal stressors. Within 1 month of starting on modafinil, he reported increased self-esteem and motivation, as well as decreased self-consciousness. The second patient was a 36-year-old woman with history of depression and a T11 ASIA grade A injury. She tried various SSRIs for depression and adjustment issues before she was started on modafinil. She lost weight and became more assertive and less self-conscious within 1 month after starting on modafinil. These 2 cases suggest that modafinil should be studied as a therapeutic option for treating lowered self-esteem in patients with SCI.