Aging of the skin is influenced both by intrinsic factors, such as chronological age, and by extrinsic or environmental factors, such as chronic ultraviolet exposure and smoking. Skin photoaging is defined as premature aging of the skin due to chronic sun exposure. Variation in human skin and hair color is due to differences in the absolute amounts and the relative proportions of black photoprotective eumelanin and red pheomelanin, which is regulated by the action of melanocortin-1 receptor (MC1R). Specific mutations in the MC1R gene are associated with distinct phenotypic features such as red hair, fair skin, and freckles. We have analyzed MC1R variants in 530 Caucasian women and have simultaneously assessed their degree of photoaging (Elfakir et al., 2010). After adjustment for possible confounders, the presence of two common variants of MC1R was identified as a risk factor for severe photoaging (adjusted odds ratio (AOR) (95% confidence interval (CI)): 2.33 (1.17–4.63)). This risk reached 5.61 (1.43–21.96) when two major diminished function variants of MC1R were present. Surprisingly, also the minor variant, V92M, was associated with increased risk of photoaging (2.57 (1.23–5.35)). In the same study, we found that two constitutive host factors were found to be independently associated with a history of facial freckles: frequent sunburns and the presence of diminished function variants of the MC1R gene. By contrast, in addition to age, five factors were independently associated with solar lentigines: constitutive host factors (dark skin color and tanning capacity), a history of freckles, sun-exposure behavior, and current intake of oral contraceptive or progestogen treatments. Surprisingly, we found an additional link between genetic variants of the MC1R gene and skin signs, i.e., the presence of two major diminished function variants of the MC1R gene was identified as a strong risk factor for sleep lines (AOR (95% CI): 8.25 (2.62–25.97)). Together, our studies confirm that genetic traits are major determinants of skin aging, and suggest that they should be considered when devising antiaging strategies.