Point defects govern many electronic and optical properties in semiconducting materials. Native defects often regulate electron-hole recombination mechanisms in, e.g., photovoltaics, whereas electrical and thermal transport properties can be tuned by controlling point defects and the resulting carrier concentrations in, e.g., thermoelectrics. The phase stability, defect formation energies, and carrier concentrations are interconnected properties of a semiconductor that are influenced by the thermodynamic environment. In particular, a thermodynamic state is defined by a fixed set of elemental chemical potentials that are determined by the impurity phases with which a material is in equilibrium. For a material in thermodynamic equilibrium, chemical potentials can vary in well-defined ranges leading to variations in material stoichiometry. Small variations in the stoichiometry of a material, as allowed by finite phase widths in composition space and associated with shifts in the thermodynamic state, cause dramatic fluctuations in defect formation energies, defect concentrations, and carrier concentrations.