Among the high-temperature intermetallic systems, transition-metal silicides are attractive because of their high melting temperatures (many greater than 2273 K) and potential oxidation resistance. In particular, Mo5Si3 exhibits a very high melting point (2453 K) and also has a solubility range of 2 – 3 atomic percent, which can aid in processing and alloy design strategies. The focus of this study is to evaluate the processing and properties of Mo5Si3 and Mo5Si3-base ntermetallics. For the optimal baseline comparison, high-purity single crystals have been fabricated, and thermal and elastic properties have been experimentally measured. Although Mo5Si3 has a strong thermal expansion anisotropy, ts elastic anisotropy factors and the Poisson's ratios indicate that Mo5Si3 is less anisotropic in elasticity. The combination of the thermal and elastic properties has been employed to calculate the thermal residual stress and to explain the potential for grain boundary cracking during processing. Room temperature Vickers indentation tests of Mo5Si3 have been performed. The orientation dependence of hardness and fracture toughness of Mo5Si3 single crystals have been obtained. The corresponding deformation and fracture modes have been revealed by microscopy studies. Finally, micro- and macroalloyed Mo5Si3 with aluminum and boron will be briefly explored with property assessments.