The adsorption of proteins onto a lipid membrane depends on and thus reflects the energetics of the underlying substrate. This is particularly relevant for mixed membranes that contain lipid species with different affinities for the adsorbed proteins. In this case, there is an intricate interplay between lateral membrane organization and the number of adsorbed proteins. Most importantly, proteins often tend to enhance the propensity of the lipid mixture to form clusters, domains, or to macroscopically phase separate. Sigmoidal binding isotherms are the typical signature of the corresponding cooperativity in protein adsorption. We discuss the underlying thermodynamic basis, and compare various theoretical binding models for protein adsorption onto mixed membranes. We also present experimental data for the adsorption of the C2A protein motif and analyse to what extent these data reflect cooperative binding.