The discovery of the HLA system as well as the progress of knowledge over several decades were based on serological methods. Today, methods of molecular biology tend to replace serological tests for HLA typing, particularly for class II alleles. However, HLA serology is still indispensable in all domains where HLA antibodies play a role. In this contribution, classical and more recently developed methods of HLA serology are described, and problems and solutions concerning the interpretation of results are discussed.