<p>Neuropsychiatric disorders are one of the leading causes of disability worldwide, placing considerable strain on healthcare systems and resulting in significant social and economic consequences. Despite the rising incidence of these disorders, their neuropathological mechanisms remain inadequately studied. In recent years, the rapid development of functional magnetic resonance imaging (fMRI) as a non-invasive brain functional imaging technology has promoted the research of neuropsychiatric disorders into a new stage. The global signal (GS) is the average signal of all gray matter voxels in the brain, which represents the overall fluctuation of the blood oxygenation level dependent (BOLD) activity across the entire brain. In addition to non-neuronal signals, GS also encompasses a significant number of neuronal signals, positioning it as a potentially crucial and valuable neuroimaging biomarker for neuropsychiatric disorders. In the current article, we first introduce the basic principles of GS and the dedifferentiation phenomenon that occurs with aging. Next, we summarize the progress of GS applications in the study of neuropsychiatric disorders and cognitive tasks, highlighting the GS topography changes observed across different conditions. Finally, we proposed future directions for further research on the dynamic changes of GS topography and its relationship with resting-state networks (RSNs). Research based on GS is expected to benefit the early identification and intervention of neuropsychiatric disorders.</p>