CFD (computational fluid dynamics) has been used to model upstream bioprocessing steps such as fermentation and homogenization. The focus of these studies has oftentimes been to characterize single-phase (liquid) flow and hydrodynamic shear. In the actual bioprocessing operations, however, there are at least two phases (cells and liquid) present. In the bioreactor, the gas bubbles constitute a third phase. More recent CFD models have considered the momentum and mass transfer that occurs between the phases. This review summarizes studies from the biochemical and biomedical literature relating to the use of CFD to model the performance of a variety of bioreactor types. Particular emphasis will be placed on describing current methods for handling multi-phase flow involving animal cells and/or gas bubbles.