In order to ensure astronauts perform well and achieve mission success, the interfaces with which they interact (hardware, software, procedures) must be well-designed. Good design depends heavily on the approach and development process followed. This chapter describes how NASA minimizes risk in design through Human Systems Integration (HSI) policies and processes. Application of HSI is illustrated through a discussion of human factors design challenges and solutions in a variety of NASA programs, including ISS, Orion MPCV, and Exploration. Case studies illustrate how an HSI approach and human factors involvement have led to successful crew interface designs.