The current case describes a 69 year old Caucasian male with a long history of untreated depressive symptoms. At age 68, the patient was started on a treatment regime for depression, but remission was not achieved. Genetic testing was performed to determine if this patient’s genetic background could help explain his resistance and suggest a more effective treatment strategy. The results of the genetic test showed variations in four pharmacodynamic-related genes, including MTHFR. These results supported the use of several medications in the current regime and indicated the addition of L-methylfolate which led to complete remission of depression symptoms.