Insomnia disorder signifies a major public health concern. The development of neuroimaging techniques has permitted to investigate brain mechanisms at a structural and functional level. The present systematic review aims at shedding light on functional, structural, and metabolic substrates of insomnia disorder by integrating the available published neuroimaging data. The databases PubMed, PsycARTICLES, PsycINFO, CINAHL and Web of Science were searched for case-control studies comparing neuroimaging data from insomnia patients and healthy controls. 85 articles were judged as eligible. For every observed finding of each study, the effect size was calculated from standardised mean differences, statistic parameters and figures, showing a marked heterogeneity that precluded a comprehensive quantitative analysis. From a qualitative point of view, considering the findings of significant group differences in the reported regions across the articles, this review highlights the major involvement of the anterior cingulate cortex, thalamus, insula, precuneus and middle frontal gyrus, thus supporting some central themes in the debate on the neurobiology of and offering interesting insights into the psychophysiology of sleep in this disorder.