The presence of sex differences in human physical performance is well-established and shaped by distinct endocrine, anatomical and physiological mechanisms. Despite sustained advances, our understanding of how inherent biological factors drive variations in exercise capacity and related pathologies is still developing. This review examines data primarily from human trials on hormonal and other physiological determinants of sex differences in exercise performance. Higher testosterone in men leads to greater muscle mass, haemoglobin, bone size and cardiac output, explaining much of the performance gap between sexes. Female physiology confers advantages during prolonged submaximal exercise, including greater fat oxidation, lower carbohydrate dependence and improved fatigue resistance, which may help explain narrower gaps in ultra-endurance events. These differences translate into a persistent performance gap (around 10%-15%) in most sports, particularly those requiring strength and power, although the gap narrows as event duration increases. Sex differences also influence responses to training and risk of exercise-related pathology, including differences in stress responses, reproductive dysfunction (e.g., hypothalamic amenorrhoea), musculoskeletal injury and thermoregulation. These insights inform specific approaches in sports medicine and clinical endocrinology, emphasising the importance of sex as a fundamental biological variable in exercise physiology, sports performance and in clinical management of athletes and those in physically demanding jobs.