The prevalence of cognitive decline and neurodegenerative diseases (e.g. stroke and dementia) is increasing. Numerous studies show that regular exercise has beneficial effects on brain health in clinical and non-clinical populations, yet adherence to public health exercise guidelines is notoriously poor. Recently, novel exercise strategies have been investigated to allow for more individualised and prescriptive approaches that target the key mechanistic pathways that allow exercise to mediate adaptation. This work exploring alternative approaches to the traditional model of exercise training has demonstrated exciting potential for positive health-related adaptations (especially for metabolic, muscle and cardiovascular function). However, few studies to date have focused on brain adaptations. The aim of this review is to summarise new and innovative interventions that have the potential to optimise exercise for improved brain health (i.e., brain structure and function). First, we will briefly summarise current understanding of the nature whereby positive effects of exercise deliver their influence on the brain (i.e., underlying mechanisms and factors affecting its delivery). We will then introduce the effects of exercise training on cognition and give examples of studies showing the beneficial effects of exercise in clinical populations. Finally, we will explore the adaptive roles of individual stressors that may induce greater health-related adaptations in the brain than exercise alone, including environmental stressors (hydrostatic stress, thermal stress and hypoxia), nutritional supplementation and cognitive loading. In summary, optimised interventions that target key mechanistic pathways linked to improved brain structure and function could ultimately protect against and/or ameliorate cognitive decline and neurodegenerative diseases. This article is protected by copyright. All rights reserved.