Cytokinin is an indispensable phytohormone responsible for a number of physiological processes ranging from root development to leaf senescence. The term “cytokinin” refers to several dozen adenine-derived compounds which occur naturally in plants, including the model plant Arabidopsis thaliana. Cytokinins (CKs) can be divided up into various classes and forms; the base forms are generally considered to be active while highly abundant cytokinin-N-glucosides (CKNGs), which are composed of a CK base irreversibly conjugated to a glucose molecule, are considered inactive. However, results from early CK studies suggest CKNGs do not always lack activity despite the perpetuation in the literature that they are inactive. Here we show that exogenous application of CKNGs to Arabidopsis tissue results in a CK response comparable to the application of an active CK base. These results are most apparent in senescence assays in which both a CK base (tZ) and CKNGs (tZ7G, tZ9G) delay senescence in cotyledons. Further physiological experiments involving root growth and shoot regeneration revealed CKNGs do not always have the same effects as CK bases, and these compounds have largely distinct effects on the transcriptome, as well as the proteome. These data are in direct contradiction to previous reports of CKNGs being inactive and raise questions about the function of these compounds as well as their mechanism of action. Because CKNGs make up the majority of CKs in Arabidopsis and other Angiosperms, it is especially important to understand their physiological effects in order to have a more holistic understanding of this essential phytohormone.