In the last two decades, a number of attempts have been made to unravel the complex genetic background of alcohol dependence. There is evidence from family, twin and adoption studies that the contribution of genetic factors accounts for 40-60% of alcohol dependence. In humans, the main approaches for investigating the complex genetics of alcoholism are linkage and association studies. Linkage studies reported alcoholism to be linked to only 5 chromosomal regions (on chromosomes 1, 7, and possibly 2, 4 and 5) and none of those loci reached a high statistical significance. Association studies are conducted by numerous research groups. They test a potential relationship between a certain genetic variant and alcoholism in a design similar to the classical case-control studies. Polymorphisms in the GABAergic, serotonergic, dopaminergic, and glutamatergic system have been related to alcohol- or alcoholism-associated phenotypes. Many studies failed to confirm initial positive results, raising doubts on the validity and replicability of this study approach. Recently more research has been conducted using genetic microarrays to investigate expression patterns of genes under the influence of chronic alcohol consumption. However, these approaches have several shortcomings, in particular their applicability in humans. In short, approaches in use for years by many research groups such as linkage and association studies showed either controversial or disappointing results. New approaches using endophenotypes and genetic microarrays may be helpful to shed light more light on the complex genetic background of alcoholism.