Objective: To systematically summarize the findings from research studies examining the effects of whole-body hyperthermia (WBH) interventions on mood and symptoms of depression. Methods: Systematic literature search of online and offline databases (e.g., Pubmed, Web of Knowledge, Cochrane, academic libraries). Risk of bias assessment and secondary analysis of effect sizes. Study selection: Clinical studies with a pre/post-intervention design and outcome measures for mood and depression as accepted in the S-3 guidelines (Association of Scientific Medical Societies in Germany). Data extraction: Study characteristics and outcomes (means and standard deviations) from participants receiving at least one WBH intervention. Results: A total of 7 studies and 148 subjects with a mean age of 46 years (36-56 years) were identified. Three out of seven studies utilized hot baths and 4/7 infrared heating. Study duration ranged from 1 to 6 weeks with one or multiple interventions and an average treatment time of 66.37 min (42.55-140). Risk of bias analysis revealed small sample biases and lack of control groups in 3/7 studies. About 21 study end-points were extracted with 19 resulting in effects sizes (Cohen's d) of 0.8 or greater. Target temperatures between 38 C and 39 C and slower increase in core body temperature during the intervention resulted in larger treatment effects. Conclusion: WBH is a promising alternative treatment for depression with low risk for adverse reactions and side effects but still lacking sufficient evidence for general recommendations for clinical practice. However, as all other interventions have failed, the studies to date can provide a framework for clinical application.