The concept of additive effect is derived from the concept of drug synergy. Thus, the origin of additive effect dates back to the early twentieth century when the search for synergy started. During the search for synergy, the models of Loewe additivity and Bliss independence were proposed. These models are capable of measuring the effects of drug combinations. Hence, Loewe additivity and Bliss independence were developed to determine whether an effect of a drug combination is synergistic or antagonistic. During the construction of these models, the concept of additive effect was introduced as the baseline for the determination of synergy and antagonism.