Noninvasive imaging of tissue perfusion is a valuable tool for both research and clinical applications. Arterial spin labeling (ASL) is a contrast-free perfusion imaging method that enables measuring and quantifying tissue blood flow using MR imaging. ASL uses radiofrequency and magnetic field gradient pulses to label arterial blood water, which then serves as an endogenous tracer. This review highlights the basic mechanism of ASL perfusion imaging, labeling strategies, and quantification. ASL has been widely used during the past 30 years for the study of normal brain function as well as in multiple neurovascular, neuro-oncological and degenerative pathologic conditions.