Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) has emerged as a powerful metabolic regulator in diverse tissues including fat, skeletal muscle, and the heart. It is now established that activation of PPARβ/δ promotes fatty acid oxidation in several tissues, such as skeletal muscle and adipose tissue. In muscle, PPARβ/δ appears to act as a central regulator of fatty acid catabolism. PPARβ/δ contents are increased in muscle during physiological situations such as physical exercise or long-term fasting, characterized by increased fatty acid oxidation. Targeted expression of an activated form of PPARβ/δ in skeletal muscle induces a switch to form increased numbers of type I muscle fibers resembling the fiber type transition by endurance training. Activation of PPARβ/δ also enhances mitochondrial capacity and fat oxidation in the skeletal muscle that resembles the effect of regular exercise. Therefore, it is hypothesized that muscle-specific PPARβ/δ agonists could be a key strategy to support the poor cardiorespiratory fitness associated with metabolic disorders.