This chapter deals with estimation of interaction through different statistical models. Interaction is classified into two different classes, antagonistic and synergistic effects. An antagonistic effect is said to be present if the combination of two factors decrease the measure of interest as compared to the expected sum of the single effect of each factor. Synergistic effect is present if the combination of two factors increases the measure of interest more than the expected sum based on each factor. Furthermore, this chapter also shows how estimation of multiplicative and additive interaction is carried out focusing on gene–environmental interaction.