In this chapter we deal with the thermodynamics of site-specific effects in Ising networks (Newell and Montroll, 1953; Hill, 1960; Stanley, 1971; Domb and Green, 1972; Itzykson and Drouffe 1989) of particular biological relevance. The basic results of the phenomenological theory described in the foregoing chapters can be merged with those of the statistical thermodynamics of model systems that have set conceptual landmarks in our understanding of cooperative phenomena. A number of important properties of biological macromolecules have been approached in terms of lattice statistics, e.g., helix-coil transitions (Zimm and Bragg, 1959; Glauber, 1963; Cohen and Penrose, 1970; Poland and Scheraga 1970), protein folding (Dill et al., 1995) and ligand-induced conformational transitions (Herzfeld and Stanley, 1974; Hermans and Premilat, 1975). These processes entail cooperative transitions involving a number of subsystems. Molecular recognition, or the process that allows proteins to interact specifically with small ligands, other proteins, RNA and DNA molecules, can be modeled in terms of the contribution of several individual recognition subsites that give rise to the macroscopic energetics measured experimentally. The properties of subsites can be modeled using Ising networks (Keating and Di Cera, 1993). A mechanistic description of cooperative processes should capture essential features which can be used eventually to develop more elaborate and accurate descriptions.