How do fibroblasts spontaneously organize into a polarized epithelial tube? This question has fascinated scientists studying the mammalian kidney for more than 40 years. The formation of epithelial tubules in the developing mammalian kidney involves both the aggregation of mesenchymal cells and their conversion into polarized epithelium, as well as the growth and branching morphogenesis of existing epithelium. The interactions among mesenchyme, epithelia and, more recently, the stroma, have been well characterized and provide novel insights into the regulatory mechanisms underlying complex organ development. Cell signaling pathways and transcription factors have been defined through genetic and biochemical assays such that a picture of early kidney tubulogenesis is beginning to emerge.