Teachers in the 21st century are facing new challenges as a result of the expanding possibilities of ICT integration in every aspect of the school milieu. Studies have shown the potential of teacher professional development (TPD) that is tailored to local conditions as well as global components and takes advantage of mutual support among teachers, as well as modeling of effective practices. The goal of the paper is to consider the issue of TPD with reference to the usage of ICT as a lever for educational change in a systemic manner, based on the application of local as well as international research. This paper will synthesize some key issues and challenges for TPD in the ICT-saturated 21st century, illustrated in four cases presented herein, which synthesize elements of practice and theory. Based on the literature and the four case studies, we suggest a conceptual model for identifying and evaluating TPD practices using ICT as a lever for educational change and innovation, accompanied by research aimed to develop TPD models. We include suggestions for more effectively linking research to practice and will lay out possible research directions, as a means of facilitating evidence-based decisions and policies.