Differentiated instruction has emerged as a research-based approach to teaching that meets the diverse needs of students based upon learner readiness, interests, and learning profile, grounded in the socio-cultural, multiple intelligences, and brain-based learning theories. The purpose of this basic qualitative inquiry was to explore teachers' perceptions and experiences with differentiation, and its impact on academic growth. Moreover, the study explored the impact of differentiation in mixed-ability classrooms. Nine general education teachers were interviewed using semi-structured questions. Inductive data analysis revealed the DI is essential and beneficial to all learners, assessment informs instruction, knowledge of multiple strategies is necessary, teacher collaboration is essential to differentiation and effective RTI, and effective classroom environment and management is essential for instruction. Data analysis also revealed teachers used the following DI strategies; flexible grouping, blended learning, project-based learning, adaptive computer software for assessments and interventions, and brain-based learning. Challenges to differentiation include lack of time for interventions and to prepare DI resources, lack of finances for differentiated equipment, and additional small group support. Despite these challenges, this exploration of teacher perceptions and experiences with differentiated instruction demonstrated DI to be beneficial in meeting the diversity of student needs. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com.bibliotheek.ehb.be/en-US/products/dissertations/individuals.shtml.]