From the conventional Fenton process (H2O2 and Fe2+), the electro-Fenton process was derived to improve the hydroxylation method (partial organic oxidation). Thereafter, electro-Fenton was adapted to water remediation. Since then, this approach has received much attention for wastewater treatment because it is an eco-friendly process and its technological implementation is simple. Although electro-Fenton involves a few and very simple chemical species (H2O2, Fe2+, Fe3+, O2), the interactions among them produce one of the most difficult set of chemical reactions. Therefore, the predictions of the main chemical reactions are a challenging task. The aim of this chapter is to propose a methodology for developing a general, practical, simple, semiempirical chemical model to predict organic pollutant abatement in a reliable electrochemical reactor by electro-Fenton process. The main outputs of this chemical model include the rate of H2O2 generation and its activation by Fe2+ to produce a strong oxidant. The organic pollutant degradation rate and the energy and time required to carry out the organic degradation are also included. Although under this approach it is not possible to follow a detailed evolution of concentration profiles of some by-products during the degradation time, this procedure is less complicated than others already available. Moreover, it can fulfil the main requirements of wastewater treatment: abatement of the organic pollutant.