Simultaneous advances in numerical methods and computing, theoretical techniques, and experimental diagnostics have all led independently to better understanding of Rayleigh-Taylor (RT) instability, turbulence, and mixing. In particular, experiments have provided significant motivation for many simulation and modeling studies, as well as validation data. Numerical simulations, in turn, have also provided data not currently measurable or very difficult to measure accurately in RT unstable flows. Thus, simulations have motivated new measurements in this class of buoyancy-driven flows. This overview discusses simulation and modeling studies synergistic with experiments and examples of how experiments have motivated simulations and models of RT instability, flow, and mixing. First, a brief summary of measured experimental and calculated simulation quantities, of experimental approaches, and of issues and challenges in the simulation and modeling of RT experiments is presented. Implicit large-eddy, direct numerical, and large-eddy simulations validated using RT experimental data are then discussed. This is followed by a discussion of modeling using analytical, modal, buoyancy-drag, and turbulent transport models of RT mixing experiments. The discussion will focus on three-dimensional RT mixing arising from multimode perturbations. Finally, this review concludes with a perspective on future simulation, modeling, and experimental directions for further research. Research in simulation and modeling of RT unstable flows, coupled with experiments, has made significant progress over the past several decades. This overview serves as an opportunity to both discuss progress and to stimulate future research on simulation and modeling of this class of hydrodynamically-unstable turbulent flows.