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Resting-state functional MRI (rs-fMRI) is an increasingly popular technique for studying brain dysfunction in psychiatric patients, and is widely assumed to measure intrinsic properties of functional brain organization. Here, we review rs-fMRI studies of psychiatric populations and consider how recent evidence concerning the neuronal basis, behavioural relevance, and the stability of rs-fMRI measures can inform and constrain interpretation of findings obtained using case–control designs.A range of rs-fMRI measures have been applied to different patient groups, although the findings have not always been consistent. The large-scale organization of rs-fMRI networks is robust and reproducible, and rs-fMRI measures show correlations with behavioural phenotypes relevant to psychiatry. However, evidence that such measures are also influenced by preceding psychological states and contexts, as well as individual variations in physiological arousal, may help to explain inconsistent findings in case–control comparisons.rs-fMRI measures show both stable and dynamic properties, the nature of which are only beginning to be uncovered. As such, interpreting significant differences between patients and controls on rs-fMRI measures as evidence for alterations in intrinsic functional brain organization should be done cautiously. Better understanding of the relationship between stable and transient aspects of spontaneous brain dynamics will be necessary to constrain interpretation of case–control studies and inform pathophysiological models.