This chapter provides fundamentals on protein chromatography. Different chromatographic media are described in terms of the solute-surface interactions that can be exploited to achieve the desired separation. Then, mechanistic models are presented to describe the three key physical phenomena involved in protein chromatography, namely the thermodynamics of fluid-solid equilibrium, the hydrodynamics and the kinetics of mass transfer. Simple methods to estimate model parameters are introduced as well as short-cut methods to design chromatographic processes. Although the main goal of this chapter is to bring theoretical basics about the modelling of protein chromatography, it is complemented by numerous experimental results for illustrative and pedagogical purposes.