Primary cancer of the liver, hepatocellular carcinoma (HCC), is an extremely deadly cancer, with very poor 5 year survivals, following diagnosis. The poor outcomes are believed to be due, in part, to the late times in which the cancers are usually first detected. Improved methods for early detection have thus become a top priority in the management of liver cancer. This Chapter reviews current methods of detection as well as leading new methods. Possible explanations as to why there are so many markers that are being discovered, but so few that make it to validation are discussed.