This chapter systematically explores the knowledge base required by teachers for the effective application of ICT in education. The Technological Pedagogical Content Knowledge (TPCK) framework and developments in associated research are reviewed. The authors suggest an alternate approach for better understanding the knowledge base required for application of ICT in education by providing a theorization about technological knowledge in relation to how a teacher realizes and actualizes the pedagogical affordances of technological tools in teaching and learning. The authors conclude that this body of knowledge cannot exist outside the frame of reference of the teacher, can be developed through systematic learning activities targeting or facilitating its development, and grows with ongoing participation or involvement in valuable professional experiences. Implications for the nature of TPCK and its development are discussed.