The synthesis of a watet-soluble polyglycerol dendrimer with two orthogonal functional groups at the core is reported. The two groups, an azide and amine group, are highly reactive toward alkyne and activated ester moieties; respectively. The orthogonality Of the two chemical reactions is demonstrated by the ability to conjugate quantitatively either :group, independent of the other and in either,order: The orthogonal functionalization of the azide- and amine cored dendrimer can be accomplished in a stepwise or a one-pot synthetic protocol. All resulting bifunctional dendrimers are fully soluble in water as the water-soluble dendritic scaffold decorated with 48 hydroxyl groups,on the surface successfully solubilizes both the hydrophobic fluorophore and targeting group: