Mathematical modeling is becoming ever more important to assess the potential, guide the design, and enable the efficient operation and control of industrial-scale microalgae culture systems (MCS). The development of overall, inherently multiphysics, models involves coupling separate submodels of (i) the intrinsic biological properties, including growth, decay, and biosynthesis as well as the effect of light and temperature on these processes, and (ii) the physical properties, such as the hydrodynamics, light attenuation, and temperature in the culture medium. When considering high-density microalgae culture, in particular, the coupling between biology and physics becomes critical. This chapter reviews existing models, with a particular focus on the Droop model, which is a precursor model, and it highlights the structure common to many microalgae growth models. It summarizes the main developments and difficulties towards multiphysics models of MCS as well as applications of these models for monitoring, control, and optimization purposes.Graphical Abstract