Fiber optic assemblies have been used on spaceflight missions for many years as an enabling technology for routing, transmitting, and detecting optical signals. Due to the overwhelming success of NASA in implementing fiber optic assemblies on spaceflight science-based instruments, system scientists increasingly request fibers that perform in extreme environments while still maintaining very high optical transmission, stability, and reliability. Many new applications require fiber optic assemblies that will operate down to cryogenic temperatures as low as 20 Kelvin. In order for the fiber assemblies to operate with little loss in optical throughput at these extreme temperatures requires a system level approach all the way from how the fiber assembly is manufactured to how it is held, routed, and integrated. The NASA Goddard Code 562 Photonics Group has been designing, manufacturing, testing, and integrating fiber optics for spaceflight and other high reliability applications for nearly 20 years. Design techniques and lessons learned over the years are consistently applied to developing new fiber optic assemblies that meet these demanding environments. System level trades, fiber assembly design methods, manufacturing, testing, and integration will be discussed. Specific recent examples of ground support equipment for the James Webb Space Telescope (JWST); the Ice, Cloud and Land Elevation Satellite–2 (ICESat- 2); and others will be included.