The goal for this special edition of Progress in Brain Research extends beyond merely probing the yet-to-be-uncovered links between physical exercise and cognitive improvement. We aim to advance our knowledge, pushing the envelope of what is currently understood. We are particularly focused on how purposefully structured physical activities, carefully chosen participant groups, and specific cognitive areas can optimize the cognitive and mental health benefits derived from physical exercise. The inaugural volume of this series introduces 3 review articles and 7 original pieces of research, encompassing both behavioral experiments and neuroimaging studies. Our focus is on experimental research that sheds light on the immediate and long-term impact of physical exercise on cognition as well as expert opinions and systematic reviews that compile current findings and suggest avenues for upcoming research.