Worldwide 284+ million people suffer from stress, anxiety and depression disorders and modern lifestyle, environments and unhealthy diets are causing an epidemic of stress, anxiety & depression (SAD) disorders. Other risk factors which contribute to SAD disorder are compromised genetics, weak immune system, low response to stress & brain neuroplasticity. Several studies had investigated genes, single nucleotide variation, Indels, large deletions, inversions & triple repeat polymorphism involved in various molecular and biological mechanisms underlying the disease initiation & progression. Recent genome-wide association studies (GWAS) have identified 150+ genes and genetic association of 44 risk variants [1, 2] for detection of SAD disorders. Nowadays At-home DNA tests (direct-to-consumer DNA tests) are gaining popularity for wellness and healthy longevity. These tests predict risk for micronutrient & vitamin deficiency, antioxidant activity, neuro-muscular functionality, risk for SAD disorders, efficacy of pharmacologically active herbal formulations for prevention & cure. On the basis of genetic outcome, medicinal plants/ herbs have been greatly employed to combat and reduce stress, anxiety & depression and thereby enhance general wellbeing in recent years. Ashwagandha (Withania somnifera, fam. Solanaceae) is a most versatile and potential herb of the Indian Ayurvedic system of medicine as a Rasayana. It is also accredited as a ‘royal herb’ having potential therapeutic applications. There are more than 33,787 publications for genetic markers for SAD & due to health awareness Ashwagandha research has gained scientific importance as evidenced by 77 publications documented since 2010 in NCBI PubMed [3]. The present review concludes with a discussion of prospects for clinical translation of genetic findings based on DNA testing, mode of action & personalized dosage of Ashwagandha as potent anti-SAD medicinal supplement