After a century of false hopes, recent studies have placed the concept of diaschisis at the centre of the understanding of brain function. Originally, the term ‘diaschisis’ was coined by von Monakow in 1914 to describe the neurophysiological changes that occur distant to a focal brain lesion. In the following decades, this concept triggered widespread clinical interest in an attempt to describe symptoms and signs that the lesion could not fully explain. However, the first imaging studies, in the late 1970s, only partially confirmed the clinical significance of diaschisis. Focal cortical areas of diaschisis (i.e. focal diaschisis) contributed to the clinical deficits after subcortical but only rarely after cortical lesions. For this reason, the concept of diaschisis progressively disappeared from the mainstream of research in clinical neurosciences. Recent evidence has unexpectedly revitalized the notion. The development of new imaging techniques allows a better understanding of the complexity of brain organization. It is now possible to reliably investigate a new type of diaschisis defined as the changes of structural and functional connectivity between brain areas distant to the lesion (i.e. connectional diaschisis). As opposed to focal diaschisis, connectional diaschisis, focusing on determined networks, seems to relate more consistently to the clinical findings. This is particularly true after stroke in the motor and attentional networks. Furthermore, normalization of remote connectivity changes in these networks relates to a better recovery. In the future, to investigate the clinical role of diaschisis, a systematic approach has to be considered. First, emerging imaging and electrophysiological techniques should be used to precisely map and selectively model brain lesions in human and animals studies. Second, the concept of diaschisis must be applied to determine the impact of a focal lesion on new representations of the complexity of brain organization. As an example, the evaluation of remote changes in the structure of the connectome has so far mainly been tested by modelization of focal brain lesions. These changes could now be assessed in patients suffering from focal brain lesions (i.e. connectomal diaschisis). Finally, and of major significance, focal and non-focal neurophysiological changes distant to the lesion should be the target of therapeutic strategies. Neuromodulation using transcranial magnetic stimulation is one of the most promising techniques. It is when this last step will be successful that the concept of diaschisis will gain all the clinical respectability that could not be obtained in decades of research.