Ions differ in their ability to salt out proteins from solution as expressed in the lyotropic or Hofmeister series of cations and anions. 
Since its first formulation in 1888, this series has been invoked in a plethora of effects, going beyond the original salting-out/salting-in 
idea to include enzyme activities and the crystallization of proteins, as well as to processes not involving proteins like ion exchange, the 
surface tension of electrolytes, or bubble coalescence. Although it has been clear that the Hofmeister series is intimately connected to ion 
hydration in homogeneous and heterogeneous environments and to ion pairing, its molecular origin has not been fully understood. This 
situation could have been summarized as follows: Many chemists used the Hofmeister series as a mantra to put a label on ion specific 
behavior in various environments, rather than to reach a molecular level understanding and, consequently, an ability to predict a particular 
effect of a given salt ion on proteins in solutions. In this Feature Article we show that, the cationic and anionic Hofmeister series can now
 be rationalized primarily in terms of specific interactions of salt ions with the backbone and charged side chain groups at the protein 
surface in solution. At the same time, we demonstrate the limitations of separating Hofmeister effects into independent cationic and anionic 
contributions due to the electroneutrality condition, as well as specific ion pairing, leading to interactions of ions of opposite polarity. 
Finally, we outline the route beyond Hofmeister chemistry in the direction of understanding specific roles of ions in various biological 
functionalities, where generic Hofmeister-type interactions can be complemented or even overruled by particular steric arrangements in 
various ion binding sites.