Hepatocellular carcinoma is the 5th most common cancer in the world. Prognosis for this disease is poor since hepatocellular carcinoma is mostly diagnosed at an advanced stage. Serum alpha-fetoprotein (AFP) is one of the most common diagnostic markers for hepatocellular carcinoma. However, its diagnostic value is more and more questioned. Therefore, research has focussed on AFP related parameters (AFP mRNA and AFP glycoforms). The aim of this paper is to review the present knowledge on AFP and its related parameters in diagnosing and monitoring HCC. AFP related parameters can be arranged in two types: AFP mRNA and AFP glycoforms. AFP mRNA is a potentially prognostic marker and AFP mRNA assays are based on PCR techniques. The AFP glycoforms have diagnostic potential and assays are based on isoelectric focussing and lectin affinity electrophoretic methods. Up to now the diagnostic use of the AFP related parameters is limited. Although some of them are recommended as a complementary test, they cannot (yet) replace serum AFP as the golden standard of diagnostic markers for hepatocellular carcinoma.