Assays of moisturizer efficacy have traditionally focused on a moisturizer's ability to alleviate dry skin. More recently, a moisturizer's ability to prevent primary irritation has been recognized. To assess and compare the ability of moisturizers to alleviate skin dryness and primary irritation, as well as prevent their return, four controlled-application clinical (in vivo) studies were carried out: hand-wash test, regression test, reduction in pre-existing irritation study, and prevention-of-irritation studies. Overall conclusions were confirmed in a home-use clinical (validation) study of people suffering from mild eczema. The controlled in vivo studies demonstrate that: (a) a moisturizer can alleviate skin dryness and irritation, and prevent their return; and (b) the efficacy of different moisturizers can be differentiated, based on their composition. The home-use study results demonstrated that the most effective moisturizer identified by the controlled-application studies was highly effective against the signs of eczema. In vivo modeling of moisturizer efficacy enables assessment and optimization of different benefits separately, while predicting the quantitative and perceived (observed) relevance of the benefits the moisturizer delivers to consumers.