This chapter focuses on Software-Defined Infrastructure, using software to optimize hardware efficiency in response to a slowing Moore’s Law. It covers software-defined servers, including compiler optimizations, hardware-aware scheduling, management of disaggregated resources, and software-defined memory. It also discusses software-defined networking, a pioneering area for these concepts, highlighting traffic and topology engineering, DDoS mitigation, bandwidth enforcement, and network-aware scheduling. Furthermore, it explores the application of ’software-defined’ approaches to accelerators and data center optimizations for power and fleet management. Finally, it concludes with machine learning’s role in optimizing control loops and future opportunities in software-defined infrastructure.