Understanding how hormones and genes interact to coordinate plant growth in a changing environment is a major challenge in plant developmental biology.Auxin,cytokinin,and ethylene are three important hormones that regulate many aspects of plant development.This review critically evaluates the crosstalk between the three hormones in Arabidopsis root development.We integrate a variety of experimental data into a crosstalk network,which reveals multiple layers of complexity in auxin,cytokinin,and ethylene crosstalk.In particular,data integration reveals an additional,largely overlooked link between the ethylene and cytokinin pathways,which acts through a phosphorelay mechanism.This proposed link addresses outstanding questions on whether ethylene application promotes or inhibits receptor kinase activity of the ethylene receptors.Elucidating the complexity in auxin,cytokinin,and ethylene crosstalk requires a combined experimental and systems modeling approach.We evaluate important modeling efforts for establishing how crosstalk between auxin,cytokinin,and ethylene regulates patteing in root development.We discuss how a novel methodology that iteratively combines experiments with systems modeling analysis is essential for elucidating the complexity in crosstalk of auxin,cytokinin,and ethylene in root development.Finally,we discuss the future challenges from a combined experimental and modeling perspective.