Memory impairment is among the most common cognitive deficits in people with multiple sclerosis (MS). To remediate this problem, recent research has evaluated the benefits of self-generated encoding. These nascent investigations reveal that people with MS who have mild memory impairment demonstrate a significant memory benefit from self-generated encoding compared with didactic learning. To extend prior research, the present experiment included MS patients with moderate–severe, rather than just mild, memory impairment. Additionally, the experiment evaluated whether self-generated encoding improves memory for activities of daily living instead of abstract words. Specifically, the experiment determined whether self-generated encoding enhanced memory for names, appointments, and object locations. In agreement with and extending prior research, MS patients remembered more information if it was self-generated rather than didactically presented, and this finding occurred despite moderate–severe memory impairment. Furthermore, compared with didactic encoding, self-generation enhanced recall of activities of daily living. Implications of these findings for cognitive rehabilitation and the nature of memory impairment in MS are discussed (JINS, 2006, 12, 640–648.)