It is well known that the strongly location-dependent microstructures observed in metal parts made using additive manufacturing (AM) processes differ from those found in components produced via traditional manufacturing processes. This is primarily because the microstructures in AM parts strongly depend on spatially-varying cooling rates that are caused by several factors including part geometry and proximity to the build plate. Consequently, it is necessary to take a fresh look into methods used for calculating resulting mechanical properties, as the increased spatial resolution that must be applied to the description of properties of AM parts calls for vast improvements in computational efficiency. Computational homogenization methods are employed for the calculation of these mechanical properties based on the polycrystalline microstructures typically encountered in metallic materials. Such calculations that enable the description of properties as a function of position increase the accuracy of a vital link in the structure–process–property–performance continuum that falls within the Integrated Computational Materials Engineering (ICME) paradigm. In this work we describe and critically review six of these methods and their application to AM microstructures. We find that the Fast Fourier Transform (FFT) method and the Finite Element Method (FEM) are the optimal choices based on several factors including accuracy, efficiency, and applicability to polycrystalline microstructures. Provided the microstructure is amenable to the use of uniform grids and the assumption of periodic boundary conditions, the FFT method has greater computational efficiency. Where unstructured meshes, adaptive remeshing and/or non-periodic boundary conditions are desired, the FEM is the method of choice. Our recommendations are equally applicable to functionally graded AM parts where site-specific microstructures are engineered using multiple materials or different process parameters. They can also be utilized for other material systems and circumstances where increased accuracy is achieved by describing mechanical properties as a function of location.