The Peroxisome Proliferator Activated Receptor alpha (PPARa) is a transcription factor that plays a major role in metabolic regulation. This review addresses the functional role of PPARa in intermediary metabolism and provides a detailed overview of metabolic genes targeted by PPARa, with a focus on liver. A distinction is made between the impact of PPARa on metabolism upon physiological, pharmacological, and nutritional activation. Low and high throughput gene expression analyses have allowed the creation of a comprehensive map illustrating the role of PPARa as master regulator of lipid metabolism via regulation of numerous genes. The map puts PPARa at the center of a regulatory hub impacting fatty acid uptake, fatty acid activation, intracellular fatty acid binding, mitochondrial and peroxisomal fatty acid oxidation, ketogenesis, triglyceride turnover, lipid droplet biology, gluconeogenesis, and bile synthesis/secretion. In addition, PPARa governs the expression of several secreted proteins that exert local and endocrine functions.