The decisive role of the epidermis in maintaining body homeostasis prompted studies to evaluate the changes in epidermal structure and functionality over the lifetime. This development, along with the identification of molecular mechanisms of epidermal signaling, maintenance, and differentiation, points to a need for new therapeutic alternatives to treat and prevent skin aging. In addition to recovering age- and sun-compromised functions, proper treatment of the epidermis has important esthetic implications. This study reviews active ingredients capable of counteracting symptoms of epidermal aging, organized according to the regulation of specific age-affected epidermal functions: (1) several compounds, other than retinoids and derivatives, act on the proliferation and differentiation of keratinocytes, supporting the protective barrier against mechanical and chemical insults; (2) natural lipidic compounds, as well as glycerol and urea, are described as agents for maintaining water-ion balance; (3) regulation of immunological pathogen defense can be reinforced by natural extracts and compounds, such as resveratrol; and (4) antioxidant exogenous sources enriched with flavonoids and vitamin C, for example, improve solar radiation protection and epidermal antioxidant activity. 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