The response of polycrystals to plastic deformation is studied at the level of variations within individual grains, and comparisons are made to theoretical calculations using crystal plasticity (CP). We provide a brief overview of CP and a review of the literature, which is dominated by surface observations. The motivating question asks how well does CP represent the mesoscale behavior of large populations of dislocations (as carriers of plastic strain). The literature shows consistently that only moderate agreement is found between experiment and calculation. We supplement this with a current example of microstructure evolution in the interior of a copper sample subjected to tensile deformation. Nondestructive measurements of orientation fields were performed using the near-field high-energy X-ray diffraction microscopy (nf-HEDM) technique at the Advanced Photon Source (APS). Starting at highly ordered grains, a single two-dimensional slice of microstructure containing 150 grains was followed through multiple strain states, where it tracked lattice rotations and defect accumulation of up to 14% elongation. In accord with the literature, at the scale of individual grains, comparison of observations with CP models indicates reasonable qualitative agreement but significant variations between simulation and experiment are apparent. The conclusion is that in order to be able to quantify the effects of microstructure on the distributions of slip, orientation change, and damage accumulation, the empirically derived constitutive relations used in continuum-scale simulations need to be improved. Equally important will be the development of large-scale simulations of polycrystals that directly model dislocations. © Copyright 2014 by Annual Reviews. All rights reserved.