Modern methods for 3D geological modeling and reservoir characterization are leading industry to routinely build very large and detailed reservoir models; grid models of the subsurface geology currently range in size from 10 to 100 million cells and are growing. Such models pose a serious computational challenge to numerical reservoir simulators. Indeed, there is a steadily increasing gap between the level of detail seen in industrial geological models and the capabilities of commercial simulators based on traditional finite-volume discretization. There are, however, several promising simulation technologies that may help bridge this gap. In this talk, I will discuss the use of geo-cellular models as direct input to flow simulation and present a family of recent multiscale flow solvers that provide efficient solution of pressure and fluid velocities on complex and strongly heterogeneous geological models. The multiscale solvers can be combined with various fast transport solvers on coarse, intermediate, and geo-cellular grids to enable reservoir simulation of million-cell models on desktop computers.