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Nanofluidics encompasses a wide range of advanced approaches to study charge and mass transport at the nanoscale. Modern technologies allow us to develop and improve artificial nanofluidic platforms that confine ions in a way similar to single-ion channels in living cells. Therefore, nanofluidic platforms show great potential to act as a test field for theoretical models. This review aims to highlight ionic Coulomb blockade (ICB)—an effect that is proposed to be the key player of ion channel selectivity, which is based upon electrostatic exclusion limiting ion transport. Thus, in this perspective, we focus on the most promising approaches that have been reported on the subject. We consider ion confinements of various dimensionalities and highlight the most recent advancements in the field. Furthermore, we concentrate on the most critical obstacles associated with these studies and suggest possible solutions to advance the field further.