Moisturization is the pillar of daily skin care and has significant benefit in improving hydration, strengthening the skin barrier, and ameliorating inflammatory dermatoses. Bioactive ingredients such as endocannabinoids, bioactive lipids, growth factors, microbiome modulators, and antioxidant enzymes are increasingly being incorporated into moisturizer formulations. These novel ingredients have been shown to improve skin barrier function, upregulate barrier lipid synthesis, decrease itch and inflammation, and have antioxidative properties. In this article, we highlight evidence supporting their mechanisms of action and efficacy in atopic dermatitis, uremic pruritus, asteatotic eczema, acne vulgaris, and vitiligo.