The muscular system of the horse is remarkable in its athletic scope and capacity to adapt to the demands placed on it. Muscular fatigue often causes exercise intolerance in horses as a primary muscular dysfunction or secondary to abnormalities in other integrated systems such as the cardiovascular, respiratory, or skeletal system. This article reviews basic muscular physiology leading to a discussion of the physiologic causes of muscular fatigue. In addition, a review of pathologic muscle disorders such as muscle strains and exertional myopathies that lead to poor performance is provided.