The environment enclosing an ionic species has a critical effect on its reactivity. In a more general sense, medium effects are not limited to the solvent, but involve the counter ion effect (ion pairing), formation of larger aggregates and structured environment as provided by the host in the case of host–guest complexes. In this review, a general view of the medium effect on anion-molecule reactions is presented. Nucleophilic substitution reactions of aliphatic (S_N2) and aromatic (S_NAr) systems, as well as elimination reactions (E2), are the focus of the discussion. In particular, nucleophilic fluorination with KF, CsF and tetraalkylammonium fluoride was used as the main model, because of the importance of this kind of reaction and the recent advances in the study of these systems. The solvent effect, ion pairing, formation of aggregates and formation of complexes with crown ethers, cryptands and calixarenes are discussed. For a deeper insight into the medium effect, many results of reliable theoretical calculations in close agreement with experiments were chosen as examples.