Photoreactions can occur in the skin when photosensitizing agents interact with ultraviolet (UV) or visible light. The term ‘photosensitization’ encompasses two main types of reaction: phototoxic and photoallergic. Phototoxic reactions, which are caused by substances applied to the skin, are also known as photo-irritant reactions. Photoallergic reactions, on the other hand, are immunologically mediated. Unlike phototoxic reactions, no detectable skin reactions occur after initial exposure to a photoallergen and UV light. It is only after an induction period that a typical delayed skin reaction results from a second exposure. Phototoxic reactions are much more common than photoallergic reactions. However, many photosensitizers are capable of causing both phototoxic and photoallergic reactions. Photosensitivity is diagnosed based on medical history, clinical and histopathological findings, as well as photodiagnostic test procedures. The most relevant photosensitizing agents are currently non-steroidal anti-inflammatory drugs, disinfectants, sunscreens, phenothiazines, and fragrances. Furthermore, porphyrins are important photosensitizing agents that can lead to clinically significant phototoxic skin reactions when exposed to UV light. The increasing use of cosmetics and toiletries, as well as the topical or systemic application of newly developed pharmaceutical products, increases consumers’ risk of exposure to unknown photosensitizing agents. Therefore, a variety of biological systems, both in vitro and in vivo, have been developed and employed. Of these, the non-radioactive modified local lymph node assay is a useful predictive test for identifying the (photo)contact sensitizing potential of chemical substances in mice.