Insufficient activity of the neurotransmitters serotonin and norepinephrine is a central element of the model of depression most widely held by neurobiologists today. In the late 1970s and 1980s, numerous studies were performed in which depressed patients were treated with the serotonin precursors L-tryptophan and 5-hydroxytryptophan (5-HTP), and the dopamine and norepinephrine precursors tyrosine and L-phenylalanine. This article briefly reviews the published research on the efficacy of neurotransmitter precursors in treating depression, highlights the findings of studies, and discusses issues regarding the interpretation of those findings. The nature of the studies makes it difficult to draw firm conclusions regarding the efficacy of neurotransmitter precursors for treating depression. While there is evidence that precursor loading may be of therapeutic value, particularly for the serotonin precursors 5-HTP and tryptophan, more studies of suitable design and size might lead to more conclusive results. However, the evidence suggests neurotransmitter precursors can be helpful in patients with mild or moderate depression.