In this chapter, the current state of the art in modeling and prediction of aerosol deposition in respiratory systems using computational fluid dynamics (CFD) is presented and reviewed. First, the physical and chemical processes governing aerosol transport, evolution, and deposition are described followed by their coupling via fundamental conservation laws. The different ways to numerically model aerosol dynamics are then described and a brief overview of the different methods that can be used to obtain a realistic geometry, computational mesh, and simulation conditions of the respiratory system is given. A short review of available numerical algorithms to solve the systems of strongly coupled partial differential equations is also presented followed by a brief discussion of the importance of proper model verification and validation. To complete the path between the inhaled aerosol and the toxicological effects, attempts to couple deterministic CFD-based aerosol deposition modeling with biological effects via physiologically based pharmacokinetic (PBPK) models are described. Finally, conclusions and the current general trends in the application of CFD to toxicological science are given.