Depression is an important and often recurrent illness. An initial 
antidepressant trial is effective at achieving remission for about 30 % of 
patients when prescribed as monotherapy, with the majority of patients returning 
as partial or non-responders. Suboptimal serum and red blood cell folate levels 
have been associated with a poorer response to antidepressant therapy, a greater 
severity of symptoms, later onset of clinical improvement, and overall treatment 
resistance. This article reviews the evidence for L-methylfolate and folic acid 
as antidepressive agents in depression and discusses their clinical use.