During the past 20 years, our work on root development has been influenced by and has contributed to three biological approaches: molecular genetics, genomics, and systems biology. Characterization of mutations that affect root radial patterning led to the identification of a transcription factor that acts as both a signaling molecule and a key developmental regulator. Combining cell sorting with microarray analysis provided a platform for determining genome-wide expression profiles of mRNAs under standard and stress conditions, revealing a vast amount of tissue-specific response. A focus on connections among molecular components identified a tissue-specific gene regulatory network and a clock-like process that determines the position of lateral roots along the primary root axis. Finally, the genetic basis for the physical network of different roots that constitutes root system architecture is being dissected using automated imaging of growing root systems.