The generation effect (GE) is a phenomenon in which material that is produced by an individual is learned and remembered better than information that is provided to that individual. The current study examined the potential benefits of self-generation on learning and memory in individuals with traumatic brain injury (TBI) and multiple sclerosis (MS). The impact of cognitive impairment on the benefits of self-generation was also examined. Subjects consisted of 18 individuals with TBI and 31 individuals with clinically definite MS. Both the TBI and MS groups recalled significantly more words in the self-generated condition versus the provided condition. Those impaired in the domains of working memory, episodic memory, or executive functioning demonstrated a significant benefit from self-generation (all ps < .05). Furthermore, although individuals with impairments in multiple cognitive domains recalled fewer words overall compared to those with no or one impaired cognitive domain, this group demonstrated a large effect size in the difference in recall for generated versus provided words. Results demonstrate that people with cognitive impairments can benefit from self-generation to improve learning and memory. Future research should focus on how to amplify the benefit of the GE for impaired groups, apply it to everyday functional tasks, and sustain its effect over time.