High-pressure die-cast (HPDC) magnesium alloys have seen diverse applications in the automotive industry, primarily driven by requirements in internal combustion engine (ICE) vehicles. As the automotive industry is transitioning to an electric vehicle (EV) architecture, there is a great potential for novel applications to improve driving range efficiency. In addition, there is a trend toward larger-sized automotive die castings and an increased interest in aerospace applications due to weight reduction. In this chapter, we reviewed the traditional automotive structural applications in ICE vehicles, as well as current and potential future EV and aerospace applications of HPDC magnesium alloys. The structural applications using AM50, AM60, AZ91 and AE44 magnesium alloys in traditional vehicles can be applied to modern EVs. Additionally, magnesium alloys with varying degrees of higher thermal conductivity, improved castability, superior high temperature properties and flammability need to be developed to replace battery and aerospace in-cabin-related structural materials to meet all safety requirements. Several newly developed magnesium alloys with superior castability are also reviewed for potential automotive and aerospace applications.