Zero-current ion transport through polymeric membranes of ion-selective electrodes (ISEs) alters the composition of the inner solution of these sensors. This causes long-term drifts of the electromotive force that are relevant for miniaturized ISEs as well as for most solid-contacted ISEs in which a thin aqueous layer is formed between the membrane and the metal electrode during conditioning. By a similar mechanism, the composition of the sample can be significantly altered during the measurement if the sample volume is small relative to the volumes of the membrane and the inner solution. This paper provides a formal model that describes the response behavior to be expected for such cases.