This paper gives a summary of different aspects for predicting protein behaviour in hydrophobic interaction chromatography (HIC). First, a brief description of HIC, hydrophobic interactions, amino acid and protein hydrophobicity is presented. After that, several factors affecting protein chromatographic behaviour in HIC are described. Finally, different approaches for predicting protein retention time in HIC are shown. Using all this information, it could be possible to carry out computational experiments by varying the different operating conditions for the purification of a target protein; and then selecting the best conditions in silico and designing a rational protein purification process involving an HIC step.