© 2018 Elsevier B.V. This systematic review explored the evidence base on the impact of listening to music on biological response in both clinical and nonclinical settings. Human studies exploring the effects of listening to recorded music on biological markers were included. Studies had to involve a non-music control condition. Keyword searches were carried out of five major databases (Cochrane/Wiley, PsycINFO, PubMed, Sage, and Science Direct) and bias was assessed using the Cochrane Risk of Bias Tool for Randomized Studies (RoB 2.0). Forty-four studies assessing the biological impact of music listening were identified: 27 in clinical settings and 17 in nonclinical settings. Eighty-two percent had examined the effects of short-term listening interventions, while the remainder had looked at longitudinal interventions. Thirteen of 33 biomarkers tested were reported to change in response to listening to music. The most commonly analyzed biomarker was the stress hormone cortisol, with half of clinical studies demonstrating a stress-reducing effect of music listening. Blood glucose was also found repeatedly to reduce in response to music listening. Many of the other biomarkers analyzed are also part of biological stress pathways, which suggests that the primary way by which music listening affects us biologically is via modulations of stress response. Effects were shown irrespective of genre, self-selection of the music, or duration of listening, although a majority did use classical music. The evidence base for understanding biological responses to music is still developing, but there is support for the application of listening to music, especially within clinical settings for stress reduction.