The conformational flexibility of a series of cage, basket, ladder, and tube polyhedral oligomeric silsesquioxanes (POSS) has been examined using the Low Mode:Monte Carlo conformational search method in conjunction with the MM3*/GBSA(CHCl3) surface. An ensemble of low energy structures was generated and used to explore the molecular shape and flexibility of each system. The results indicate that, except for the ladder molecule, the incompletely condensed systems that are studied are relatively rigid. Even in cases where the molecule is able to adopt numerous low energy conformations, the overall shape remains cage-like and the conformations differ only by small angles or substituent orientations. The ladder molecule is the most flexible and this ensemble clusters into two families: one that is cage-like and the other that is more open and ladder-like. The conformational flexibilities in the gas and solvent phases, as approximated using the GBSA continuum solvent model, are very similar.