Initial investigations on dopamine D4 receptors generated much interest in the role of this receptor in schizophrenia and other aspects of human behavior, as well as new opportunities for novel therapeutics. However, attempts to treat patients suffering from schizophrenia with dopamine D4 agents have failed to yield satisfactory results so far. An examination of the dopamine D4 literature shows that contrasting and conflicting data seemed to be the norm in this field of research. This paper reviews the literature on the dopamine D4 receptor and discusses many of the associated methodological problems that might have contributed to the paradoxical findings.