Ion channels are hollow proteins that have evolved to exhibit discrimination between charged solutes. This property, known as ion selectivity is critical for several biological functions. By using the bacterial porin OmpF as a model system of wide protein channels, we demonstrate that significant insights can be gained when selectivity measurements are combined with electrodiffusion continuum models and simulations based on the atomic structure. A correct interpretation of the mechanisms ruling the many sources of channel discrimination is a first, indispensable step for the understanding of the controlled movement of ions into or out of cells characteristic of many physiological processes. We conclude that the scattered information gathered from several independent approaches should be appropriately merged to provide a unified and coherent picture of the channel selectivity.