The creation or discovery of animal models of psychiatric conditions, such as major depressive disorder, is fraught with many problems that are not encountered in the development of models in other areas of medicine. Some of these problems are the result of the apparent nature and complexity of the symptoms presented by the psychiatric patient. However, other problems reflect philosophical positions ranging from those based on the premise that primary depression does not fit the medical model and therefore is not a “disease” that can be modeled, to those holding that the emotional state of depression is so uniquely human that subhuman organisms cannot be used in its analysis. In evaluating animal models of any human disorder or condition, it is crucial for those using the models to keep abreast of developments and advances in the relevant clinical knowledge concerning the particular condition being studied. This is especially important for such disorders as essential hypertension or major depression where the central causative factors are not yet known, but where extensive clinical investigation is constantly expanding knowledge of the patients’ condition.