Fundamental concepts governing ion selectivity in narrow pores are reviewed and the microscopic factors responsible for the lack of selectivity of the NaK channel, which is structurally similar to the K + -selective KcsA channel, are elucidated on the basis of all-atom molecular dynamics free energy simulations. The results on NaK are contrasted and compared with previous studies of the KcsA channel. Analysis indicates that differences in hydration of the cation in the pore of NaK is at the origin of the lack of selectivity of NaK.