Sunscreens have become since more than 40 years the most popular means of protection against UV radiation (UVR) in Western countries. Organic and inorganic filters with different absorption spectrum exist. They filter or scatter UVR. Protection from UVB is quantified as a minimal erythema dose-based sun protection factor. UVA protection testing is less standardized: Persistent pigment darkening and critical wavelength are currently used methods. Marketing and labeling of sunscreens underlay national regulation which explains major differences between the European and the US sunscreen market. Sunscreens are most performing in sunburn prevention. Broad spectrum UVB and UVA protection and regular application in sufficient amounts are essential for prevention of skin cancers, UV-induced immunosuppression, and skin aging. A significant benefit from regular sunscreen use has not yet been demonstrated for primary prevention of basal cell carcinoma and melanoma. Concerning the prevention of actinic keratoses, squamous cell carcinomas, and skin aging, the effect of sunscreens is significant, but it remains incomplete. Some organic UV filters (PABA derivatives, cinnamates, benzophenones, and octocrylene) have been described to cause photoallergy. Percutaneous absorption and endocrine disrupting activity of small-sized organic and nano-sized inorganic UV filters have been reported. On lesional skin and in pediatric settings, these products should be used with caution. Cutaneous vitamin D synthesis depending on skin-carcinogenic UVB radiation, the potential risk of vitamin D deficiency by sunscreen use has become a major subject of public health debate. Sunscreens indeed impair vitamin D synthesis if they are used in the recommended amount of 2 mg/cm2, but not in lesser thickness below 1.5 mg/cm2 that corresponds better to what users apply in real life conditions. Large molecular last generation UVB-UVA broad spectrum sunscreens have a better benefit-risk ratio than former organic filters: They offer better protection in the UVA band, they are non toxic and non allergenic. A better outcome of sunscreen efficacy especially in primary skin cancer prevention may be achieved with these molecules.