Auxin regulates a broad spectrum of developmental processes, mediating transcriptional regulation via protein degradation. The molecular mechanisms of auxin action are partially understood whereas the molecular basis for developmental specificity in auxin responses is currently unclear. Recent biochemical and chemical-genetics studies have narrowed the search for regulators in auxin signaling that act upstream of auxin-dependent protein degradation. The auxin response requires the degradation of Aux/IAA inhibitors, which causes interacting ARF transcription factors to be released to regulate target genes. There are many ARFs and Aux/IAA proteins in Arabidopsis, and recent genetic studies suggest that their cell-specific combinations may determine the various auxin responses in development.