The world Health Organization defines health as complete well-being in terms of physical, mental and social, and not merely the absence of disease. To attain this, individual should adapt and self-mange the social, physical and emotional challenges of life. Exposure to chronic stress due to urbanization, work stress, nuclear family, pollution, unhealthy food habits, lifestyle, accidental death in the family, and natural calamities are the triggering factors, leading to hormonal imbalance and inflammation in the tissue. The relationship between stress and illness is complex; all chronic illnesses such as cardiovascular disease and asthma have their root in chronic stress attributed by inflammation. In recent times, yoga therapy has emerged as an important complementary alternative medicine for many human diseases. Yoga therapy has a positive impact on mind and body; it acts by incorporating appropriate breathing techniques and mindfulness to attain conscious direction of our awareness of the present moment by meditation, which helps achieve harmony between the body and mind. Studies have also demonstrated the important regulatory effects of yoga therapy on brain structure and functions. Despite these advances, the cellular and molecular mechanisms by which yoga therapy renders its beneficial effects are inadequately known. A growing body of evidence suggests that yoga therapy has immunomodulatory effects. However, the precise mechanistic basis has not been addressed empirically. In this review, we have attempted to highlight the effect of yoga therapy on immune system functioning with an aim to identify important immunological signatures that index the effect of yoga therapy. Toward this, we have summarized the available scientific evidence showing positive impacts of yoga therapy. Finally, we have emphasized the efficacy of yoga in improving physical and mental well-being. Yoga has been a part of Indian culture and tradition for long; now, the time has come to scientifically validate this and implement this as an alternative treatment method for stress-related chronic disease.