Additive Manufacturing (AM) is touted as an innovative process that is leading a revolution in manufacturing. Even though it is widely hyped, its widespread adoption will be endangered until fundamental materials issues leading to large uncertainty in properties and wide variability in performance are addressed. Even in existing material systems, challenges arise from the use of metal powders as the prominent feedstock and the unique conditions inherent in fusion-based additive manufacturing processes. Powders are prone to the pick-up of interstitial elements, such as nitrogen and oxygen, and become susceptible to large changes in transformation behavior with small variations in minor alloying elements. These alloying element variations, even within allowable specified limits, impact the microstructural evolution during AM processing and post-process heat treatments in the complex multi-component alloy systems in common use. New alloy development, with an emphasis on materials designed specifically for AM processing, appears to be the preferred route to addressing these challenges. Such an ambitious goal is driven, in part, by the emergence of a range of new combinatorial and digital tools that allow complex alloying element interactions to be captured in previously unobtainable detail. This approach is not particularly applicable in the short and medium term, given the long development and validation cycles for new materials. In the short term, these tools can be utilized on existing systems to develop more flexible approaches to manufacturing by adapting material compositions to post processing in order to achieve consistent properties and performance for AM components.