Improved therapeutic options for hepatocellular carcinoma and metastatic disease place greater demands on diagnostic and surveillance tests for liver disease. Existing diagnostic imaging techniques provide limited evaluation of tissue characteristics beyond morphology; perfusion imaging of the liver has potential to improve this shortcoming. The ability to resolve hepatic arterial and portal venous components of blood flow on a global and regional basis constitutes the primary goal of liver perfusion imaging. Earlier detection of primary and metastatic hepatic malignancies and cirrhosis may be possible on the basis of relative increases in hepatic arterial blood flow associated with these diseases. To date, liver flow scintigraphy and flow quantification at Doppler ultrasonography have focused on characterization of global abnormalities. Computed tomography (CT) and magnetic resonance (MR) imaging can provide regional and global parameters, a critical goal for tumor surveillance. Several challenges remain: reduced radiation doses associated with CT perfusion imaging, improved spatial and temporal resolution at MR imaging, accurate quantification of tissue contrast material at MR imaging, and validation of parameters obtained from fitting enhancement curves to biokinetic models, applicable to all perfusion methods. Continued progress in this new field of liver imaging may have profound implications for large patient groups at risk for liver disease.