Most micro-mesoporous adsorbents used in practical adsorptive fluid (gas and liquid) separation processes are energetically heterogeneous. The adsorbent heterogeneity plays a significant role in establishing the shapes of the equilibrium adsorption isotherms (pure component or mixture), the corresponding heats of adsorption, and the adsorbate mass-transfer rates, which in turn determine the overall separation performance by a process. The sources of the adsorbent heterogeneity are discussed, and the pros and cons of several analytical heterogeneous models describing pure and multi-component adsorption isotherms, heats, and adsorbate mass-transfer coefficients are analyzed. Several critical effects of the adsorbent heterogeneity on the equilibrium isotherms are presented with examples to describe the complexity of the subject. The overall effect of adsorbent heterogeneity on an adsorptive process performance will, of course, depend on the specific adsorbate-adsorbent-process design combination. The results of a model simulation for the performance of a pressure swing adsorption process designed to separate a bulk gas mixture (C2H4 + He) using a heterogeneous adsorbent (BPL activated carbon) is briefly presented as an example. The simulation shows that the separation performance deteriorates as the degree of the adsorbent heterogeneity is increased. Extensive experimental verification of the equilibrium and the kinetic models for a heterogeneous adsorbent and the subsequent separation process performance in a pilot- or commercial-scale plant are required to confirm the actual performance by a heterogeneous adsorbent.