A major achievement of the first twenty years of neuroimaging is to reveal the brain networks that underlie fundamental aspects of attention, memory and expertise. We examine some principles underlying the activation of these networks. These networks represent key constraints for the design of teaching. Individual differences in these networks reflect a combination of genes and experiences. While acquiring expertise is easier for some than others the importance of effort in its acquisition is a basic principle. Networks are strengthened through exercise, but maintaining interest that produces sustained attention is key to making exercises successful. The state of the brain prior to learning may also represent an important constraint on successful learning and some interventions designed to investigate the role of attention state in learning are discussed. Teaching remains a creative act between instructor and student, but an understanding of brain mechanisms might improve opportunity for success for both participants.