Structural and functional aspects of the hippocampus have been shown to be sensitive to the aging process, resulting in deficits in hippocampal-dependent cognition. Similarly, adult hippocampal neurogenesis (AHN), described as the generation of new neurons from neural stem cells in the hippocampus, has shown to be negatively affected by aging throughout life. Extensive research has highlighted the role of physical exercise (PE) in positively regulating hippocampal-dependent cognition and AHN. Here, by critically reviewing preclinical and clinical studies, we discuss the significance of PE in reversing age-associated changes of the hippocampus via modulation of AHN. We indicate that PE-induced changes operate on two main levels. On the first level, PE can potentially cause structural modifications of the hippocampus, and on the second level, it regulates the molecular and cellular pathways involved. These changes result in the vascular remodelling of the neurogenic niche, as well as the secretion of neurotrophic and antioxidant factors, which can in turn activate quiescent neural stem cells, while restoring their proliferation capacity and boosting their survival - features which are negatively impacted during aging. Understanding these mechanisms will allow us to identify new targets to tackle cognitive aging and improve quality of life.