Objective: This is the second of two articles reviewing the modern dietary technique of acute tryptophan depletion (ATD), a method of transiently reducing central serotonin levels in both healthy volunteers and clinical populations. This article details the clinical studies to date and discusses the implications of this research methodology. Method: The authors present a review of clinical ATD studies collated from a MEDLINE search, unpublished communications and the authors' considerable experience with this paradigm. Results: Following from the initial use of ATD in subjects with depressive illness, studies of anxiety disorders and other psychiatric illnesses have been reported. Sleep, aggressive and cognitive effects are also active areas of research and are reviewed here. Conclusions: Acute tryptophan depletion remains a useful psychiatric research tool. The findings from the clinical studies reviewed here are summarized and implications for future research detailed.