Clay-modified electrodes (CLMEs) have received attention in the development of electrochemical sensors and biosensors. This article reviews the use of CLME for these electroanalytical purposes. It includes an introduction to the structure of cationic and anionic clays, an overview of electron transfer occurring at CLME, and of the different modes of preparation of CLME. The analytical applications reported for CLME range from the preconcentration method applied to the detection of cationic species (i.e., metal cations) or organic molecules (i.e., water pollutants and drugs), to electrocatalytic sensors involving intercalated redox mediators in the electrochemical detection process, and finally to amperometric and potentiometric biosensors. Several enzymes have been immobilized within clay matrices and amperometric biosensors based on CLME are presented following the three modes of detection referred to as first, second, and third generation of biosensors, depending on the nature of the enzymes.