Auxins are plant hormones that regulate a broad range of biological processes, including embryogenesis, stem elongation, leaf formation and fruit development. These tryptophan-like small molecules elicit their physiological responses by binding to the F-box–containing transport inhibitor response 1 (TIR1) family of proteins and causing the degradation of the auxin/indole-3-acetic acid (Aux/IAA) family of transcriptional repressors. The exact mechanisms by which auxins regulate so many different processes in plants is not clear, and studying this system is challenging because there are six TIR1/Auxin-signaling F-box (TIR1/AFB) proteins and 29 known Aux/IAA proteins in Arabidopsis thaliana. Estelle and colleagues used several techniques, including in vitro auxin-binding assays, yeast two-hybrid and plant growth assays, to show that the TIR1/AFB proteins and the Aux/IAA proteins act as co-receptors for auxin, with dramatically different binding affinities and dose-response relationships, depending on which TIR1/AFB–Aux/IAA pair was studied. It seems likely that some TIR1/AFB–auxin–Aux/IAA complexes form at a very low intracellular auxin concentration in vivo, whereas other complexes do not assemble until the intracellular auxin concentration exceeds a specific value. This suggests that different TIR1/AFB–Aux/IAA pairs may regulate different physiological processes in plants. Additional research is needed to determine which of the 174 possible TIR1/AFB–Aux/IAA pairs actually form in vivo and to elucidate how the formation of a specific TIR1/AFB–auxin–Aux/IAA ternary complex leads to a specific physiological event. (Nat. Chem. Biol. doi:10.1038/nchembio.926, published online 1 April 2012)