Post deposition annealing of supported films not only can induce transformation to a different phase but also can promote ion diffusion across the film-substrate interface with subsequent chemical reaction at that interface. Such interfacial processes have been observed in zinc oxide films deposited on borosilicate glass or vitreous silica substrates when heated to temperatures exceeding 675 K. Raman measurements acquired as a function of temperature show gradual transformation to a zinc berate or silicate phase with concomitant change in dielectric properties. Analogous reactions have been observed for zinc oxide films deposited on sapphire substrates. Spectroscopic ellipsometry and Raman spectroscopy are used to characterize the film-substrate interaction at the buried interface for ZnO and doped ZnO films subjected to post deposition annealing. Films studied are either amorphous, consist of randomly oriented wurtzite crystalline grains, or are highly c-axis oriented wurtzite, depending upon the deposition method. It is shown that above a critical temperature, not only substrate interactions occur, but resident cation dopants also can chemically react with the zinc oxide matrix. Such reactivity can significantly limit the effects such dopants have on the optical and conductivity properties of ZnO.