In psychiatric pharmacotherapy, there are many undesirable events which can exacerbate patient QOL (quality of life) such as side effects, difficulty of therapeutic effect prediction and prolongation of treatment duration in treatment-resistant cases. To resolve these problems, it has been very important to establish treatment and predictive markers which can be utilized in pharmacotherapy. In this respect, recent studies have been carried out to demonstrate endophenotype in schizophrenia. Endophenotype is an alternative marker based on genetics, and it can contribute to the assessment of disease by indicating a complicated pathology such as depression. However, the application of endophenotype to depression pharmacotherapy has not been well shown. In this paper, on the subject of neurotransmitter metabolites, vitamin B groups, homocysteine, S-100B and PET (positron emission topography), we scrutinized the relevance to depression or depression therapeutic agents and the validity of the application of endophenotypes to depression pharmacotherapy. In addition, we suggested the significance of endophenotype utilization for improvement of depressive patient QOL by prediction of therapeutic or side effects and patient adherence to instructions by a pharmacist.