While cut-rent thermodynamic models are satisfactory for the description of many systems of industrial interest, then are other mixtures for which specialized modeling techniques are needed. Mixtures containing associating and hydrogen-bonding species, and the complicated phase behavior of highly nonideal mixtures are two examples of mixtures that are difficult to describe accurately. Here, we consider recent advances in predicting the phase behavior of such mixtures. In particular, we will show how molecular orbital calculations can be used to aid in the description of the phase behavior of pure fluids and mixtures containing hydrogen-bonding components. The description of highly nonideal mixtures over large ranges of temperature and pressure has traditionally been a difficult thermodynamic problem. Here we will show how recent combinations of excess free energy models and equations of state provides better modeling tools for this problem using examples from vapor-liquid and liquid-liquid equilibria, and critical region behavior.