Britton Chance has pioneered magnetic resonance spectroscopy (MRS) and near-infrared (NIR) spectroscopy (NIRS) as noninvasive methods for measuring muscle metabolism in vivo from the late 1970s. This review honoring Britton Chance will highlight the progress that has been made in developing and utilizing MRS and NIRS technologies for evaluating skeletal muscle O2 dynamics and energetics. Adaptation of MRS and NIRS technology has focused on the validity and reliability of the measurements and extending the methods in physiological and clinical research. Britton Chance has conducted MRS and NIRS research on elite athletes and a number of chronic health conditions, including patients with chronic heart failure, peripheral vascular disease, and neuromuscular myopathies. As MRS and NIRS technologies are practical and useful for measuring human muscle metabolism, we will strive to continue Chance's legacy by advancing muscle MRS and NIRS studies.