The two most common methods for measuring perfusion with MRI are based on dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL). Although clinical experience to date is much more extensive with DSC perfusion MRI, ASL methods offer several advantages. The primary advantages are that completely noninvasive absolute cerebral blood flow (CBF) measurements are possible with relative insensitivity to permeability, and that multiple repeated measurements can be obtained to evaluate one or more interventions or to perform perfusion-based functional MRI. ASL perfusion and perfusion-based functional MRI methods have been applied in many clinical settings, including acute and chronic cerebrovascular disease, CNS neoplasms, epilepsy, aging and development, neurodegenerative disorders, and neuropsychiatric diseases. Recent technical advances have improved the sensitivity of ASL perfusion MRI, and increasing use is expected in the coming years. The present review focuses on ASL perfusion MRI and applications in clinical neuroimaging.