Isoelectric focusing (IEF), which is classified by Giddings as an equilibrium gradient method (EGM), is widely considered to be the most powerful technique available for protein separations. Prior to 1985, IEF was the only known electrophoretic EGM but was joined in that year by O'Farrell's Counter-Acting Chromatographic Electrophoresis (CACE). Since that time, more than a dozen new electrophoretic EGMs have been identified, including electric field-gradient focusing and thermal gradient focusing, and it is expected that dozens more may soon join this list.

This paper will begin with a general overview of gradient methods followed by a description of recent advances in this field. I will conclude by suggesting how a new members of the family of orthogonal EGMs might be developed.