Two recent evolutions in computing architectures, CompactPCI Serial (PICMG CPCI S.0) and VPX (ANSI-VITA 46.0), set out to meet the increasing demands of serial interfaces in harsh embedded computing environments. Both standards offer unique attributes and application-specific advantages, depending on system complexity, available budget and environmental requirements of an application. This paper describes the nuances of each that designers should consider when deciding on which to use in an application. A historical perspective detailing the evolution of each is also provided.