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Three-dimensional (3D) constructive interference in steady state (CISS) is a gradient-echo MRI sequence that is used to investigate a wide range of pathologies when routine MRI sequences do not provide the desired anatomic information. The increased sensitivity of the 3D CISS sequence is an outcome of the accentuation of the T2 values between cerebrospinal fluid (CSF) and pathological structures. Apart from its well-recognized applications in the evaluation of the cranial nerves, CSF rhinorrhea and aqueduct stenosis, we have found the CISS sequence to be useful for the cisternal spaces, cavernous sinuses and the ventricular system, where it is useful for detecting subtle CSF-intensity lesions that may be missed on routine spin-echo sequences. This information helps in the management of these conditions. After a brief overview of the physics behind this sequence, we illustrate its clinical applications with representative cases and discuss its potential role in imaging protocols.