The relationship between mnemonic instruction and academic performance for secondary-school-age youth with disabilities was explored in this systematic review. A total of 20 studies intervening with 669 youth with learning disabilities, emotional and behavioral disorders, and mild developmental disabilities were reviewed. The findings of this review strongly support the efficacy of mnemonic interventions across study methods, educational settings, student ages, and disabilities in the improvement of academic performance, typically measured by recall of word meanings or factual information. A series of detailed implications for practice is discussed and reference is made to specific literature providing detailed descriptions of mnemonic interventions.