It has been well documented that sunlight is the main carcinogen involved in the formation of skin cancer. The worldwide incidence of which is increasing and from epidemiological studies that the long-term use of sunscreens is beneficial. The wide range of ultraviolet (UV) filters used to protect the skin from UV consists of either organic molecules and/or metal oxides (including micro- or nano-sized particles). Formulations also contain synthetic compounds and naturally-derived materials which may cause allergic reactions, thereby preventing their use by some people. While the erythemal protective effect of sunscreens is easy to measure, their immunosuppressive effects are not so. Recent regulatory changes and the consumer desire for naturally-derived formulations are driving extensive re-formulation of sun protection products. Thus, there is an increasing need to be able to quickly and effectively screen any new formulations and their components for toxicity and allergic reactions. Recently an Immune Balance Rating (IBR) has been devised to provide a more efficient and evidence-based development of such additives with optimal hypoallergenic and immunoprotective properties. The results from five product indicators (Immunostimulation, Immunosuppression, Phototoxicity, Protection against UV damage, and Protection against UV immunosuppression) are aggregated and an overall IBR for an ingredient or formulation is derived. We have validated the IBR using in vitro human cell systems, which allows for the evaluation of direct cytotoxic, immune and phototoxic effects of the additive itself, as well as their protective properties against UV-induced photoageing and UVA-immunosuppression. Recent findings concerning the bioactivities of organic UV blockers and metal oxide particles in this screening system will be discussed to show how the IBR can be used to eliminate unsuitable formulations before human trials.