This review deals with the use of pyridine-nucleotide dependent dehydrogenase enzymes in amperometric biosensor design. The electrochemistry of the nicotinamide coenzymes, their mechanism and the challenges associated with their direct oxidation on solid electrodes are discussed. In addition, a survey of the different solutions proposed in the literature for addressing these problems and some of their applications are presented.This article provides an overview of the challenges associated with the direct oxidation of the pyridine-coenzymes on solid electrodes, the different solutions proposed in the literature and the application of these enzymes to the design of amperometric biosensors.