An energy input is often required to promote chemical reactions. Although heat is commonly applied to overcome activation barriers in such processes, other forms of energy can also be utilized to unlock chemical potential. Light, electricity and mechanical force can facilitate chemical transformations, and these strategies can also benefit from technological advancements in reactor design and the integration of flow processes. Although these approaches have been investigated since the 19th century, they are enjoying a resurgence and now find mainstream and diverse synthetic applications. Improvements have generally coincided with conceptual and technological developments, and this Review showcases recent advances aligned with themes spanning photoredox catalysis, mechanochemistry, electrosynthesis and synthesis in static electric fields and in flow.