This chapter examines the challenges to 21st century content preparation and pedagogy from the perspective of teaching professionals from different African countries: Cameroon, Ghana, South Africa, Lesotho and Zimbabwe. Specifically, the chapter explores the views and experiences of the participants during and after teacher preparation programs. Findings reveal common challenges, specific 21st century skills that are overlooked, and those not yet fully integrated in teacher preparation programs. The chapter offers suggestions for improvement based on the views of participants, research-based literature review, and best practices in teacher preparation programs.