Breaking water-in-oil emulsions during the refining of crude oils is an important step before any upgrading process is started. Asphaltene molecules are incriminated as playing an important role in this phenomenon. Unraveling the mechanisms behind the affinity between them and water is a key step to understand how to break these emulsions more easily and require lower amounts of demulsifiers. Choosing which demulsifier molecule(s) to use is also primordial, but to do so rationally, one needs to know which are the molecular interactions in place between asphaltenes, porphyrins and water so that demulsifiers are chosen to destabilize a specific physical–chemical interaction. In this paper, we study the interactions arising between asphaltenes and porphyrins and six different molecules potentially displaying a demulsification action in the presence of water/oil interfaces. We demonstrate that the ionic demulsifier molecules present an interesting potential to either interact strongly with water, replacing asphaltenes in this interaction, or to interact with the active sites of asphaltenes, deactivating them and avoiding any asphaltenic interfacial activity. Finally, we also found that although asphaltenes do not migrate spontaneously toward the water/oil interfaces, porphyrins do so rather easily. This indicates that porphyrins do have an important activity at the water/oil interface.