Branching morphogenesis involves the restructuring of epithelial tissues into complex and organized ramified tubular networks. Early rounds of branching are controlled genetically in a hardwired fashion in many organs, whereas later, branching is stochastic, responding to environmental cues. We discuss this sequential process from formation of an organ anlage and invagination of the epithelium to branch initiation and outgrowth in several model systems including Drosophila trachea and mammalian lung, mammary gland, and kidney.