Differentiated instruction is becoming critical in higher education due to student diversity and background knowledge. Differentiated instruction does not mean matching teaching styles with learning styles as suggested by the learning styles theory. Findings in recent research studies have proved the lack of credible evidence for the utility of the learning styles theory. As not scientifically proven, the theory serves to perpetuate the learning styles mythology in the educational psychology world. This paper will emphasize students' readiness levels as a critical part of differentiated instruction that teachers should refer to rather than sticking to student preferences and/or learning styles. The paper also suggests strategies to differentiate instruction effectively. These strategies include, but are not limited to, identifying student readiness; making modifications of the instructional content, process, and product; and enhancing collaboration and autonomy in learning. The last part of the paper places an emphasis on the integration of teaching and practice. Differentiated instruction, at its best, should reflect a new pedagogy that can promote practical integration and knowledge transformation. If implemented thoroughly, differentiated instruction can demonstrate institutional effectiveness and equip students with diverse learning experiences to highly respond to increased challenges in the global society.