Review article that attempts to highlight some recent discoveries evidencing the important role which lone-pair–pi interactions, and anion–pi interactions in particular, play in stabilizing structure and affecting function of biomolecules. Special attention is paid to studies exploring the physical origin of these at first glance counterintuitive interactions between a lone-pair of electrons of one residue and the pi-cloud of another residue. Recent theoretical work went beyond the popular electrostatic model and inquired to which extent orbital interactions have to be taken into account. At least in one biologically relevant case- in that of anion-flavin interactions- a substantial charge-transfer component has been shown to operate.