The role of the inert (lone) pair of electrons in thallium(I) salts is studied by comparison of the compounds [TI@18-crown-6]X-+(-) (X = TlI4, ClO4) and [K@18-crown-6]+ClO4- In contrast to common introductory chemistry textbook opinions, the paradigm that s-p hybridization is a prerequisite for an inert electron pair to become stereochemically active in compounds of the heavier main group elements has to be revised. Instead, an inert pair of electrons is expected to become stereochemically involved whenever it is forced to participate in antibonding orbital interactions with its surroundings, and there is the possibility for a structural distortion that minimizes these repulsive forces. The structural distortion will occur to such an extent that repulsive orbital interactions and attractive electrostatic interactions counterbalance. Our results also provide an explanatory background for many of the rules of thumb that are found in the literature about why and when an inert electron pair is expected to become stereochemically active in a certain compound.