Employing detailed atomistic modeling we elucidate the mechanisms 
behind ion-binding to proteins and other bio-molecules and
conclude that (1) small, hard ions bind via direct ion-pairing to charged surface groups and (2) large, 
soft ions bind to non-polar
groups via a solvent assisted attraction. Our predictions are in qualitative agreement with 
bulk electrolyte data and may provide an
important clue for the basic understanding of ion-specific effects in biological systems.