This talk will focus on the development of advanced thermoelectric materials within the Materials Genome Initiative paradigm.  These efforts are driven by a close coupling of theory, computation, and experimental validation.  Our implementation of a high through-put search of known and hypothetical compounds for thermoelectric performance (NSF-DMREF) has led to the identification of new classes of materials with promise for thermoelectric performance.  Further refinement of the search has recently involved: (a) identifying defects and alloying species with exceptionally strong phonon-point defect scattering cross-sections, (b) efficient routes to estimate phonon-phonon coupling strength, and (c) addressing thermoelectric performance in magnetic systems. Together, these efforts form the backbone of a material discovery program dedicated to enabling significant advancements in thermoelectric performance.  The applicability of these techniques to other functional materials will be discussed (e.g. transparent conducting oxides, thermal barrier coatings).