Heme-thiolate proteins (HTPs) play critical biological roles by catalyzing challenging chemical reactions. The ability of HTPs to selectively oxidize inert substrates under mild conditions has led to much research aimed at the development of useful in vitro oxidation technology. Very complex electron transfer machinery is required to support HTP chemistry, and electrochemical methods provide many of the needed components. The challenge is to find a system that has good electrode-enzyme electronic coupling that, in turn, would drive catalytic turnover at relatively high rates. Several systems reviewed herein have shown promise in experimental work on components that could be part of a molecular machine for the selective oxidation of organic substrates. (c) 2005 Elsevier Inc. All rights reserved.