S-adenosylmethionine (SAM-e) is a compound naturally produced in the body and is involved in methylation reactions, which affect neurotransmitter synthesis and regulation. SAM-e has been most extensively studied for its potential role in treating depression and osteoarthritis. Its use for "stress" is less well-studied and is largely extrapolated from its antidepressant effects. Several randomized controlled trials and meta-analyses have shown that SAM-e can be effective for mild to moderate depression, with efficacy comparable to some conventional antidepressants. Since stress and depression can share overlapping symptoms and neurochemical pathways, some clinicians and individuals use SAM-e to support stress management, hoping to improve mood and resilience to stressors. However, there are no robust clinical trials directly studying SAM-e for the treatment or prevention of stress in otherwise healthy individuals. Therefore, while there is some scientific evidence for mood support, the specific use of SAM-e for stress is supported only indirectly, and the evidence is limited. The overall strength of the evidence for SAM-e in stress-related conditions is modest and warrants further research.