Conformation constitutes a vital property of biomolecules, especially in the cases of enzymes and aptamers, and is essential in defining their molecular recognition ability. When biomolecules are immobilized on electrode surfaces, it is very important to have a control on all the possible conformational changes that may occur, either upon the recognition of their targets or by undesired alterations. Both enzymes and aptamers immobilized on electrodes are susceptible to conformational changes as a response to the nature of the charge of the surface and of the surrounding environment (pH, temperature, ionic strength, etc.). The main goal of this review is to analyze how the conformational changes of enzymes and aptamers immobilized on electrode surfaces have been treated in reports on biosensors and biofuel cells. This topic was selected due to insufficient information found on the actual conformational changes involved in the function of these bioelectrochemical devices despite its importance.