Contact with external irritating agents such as dishwashing liquid, formaldehyde, or raw meat may result in irritant contact dermatitis (ICD), a localized nonimmunologic condition. ICD ensues when irritant stimuli overpower the defense and repair capacities of the skin [34, 86]. Exposure to highly potent irritants or exposure to mild irritants for an extended period of time will increase the likelihood of developing ICD. Prevention of skin irritation is the main therapeutic strategy in irritant dermatitis. The causative irritant should be avoided, in addition to other common environmental irritants such as soaps and detergents. Regular use of emollients and the use of syndets or non-soap cleansers help to maintain the skin barrier. Protective clothing such as gloves, can reduce skin contact with environmental irritants while allowing the skin to heal. It is important that protective clothing be suitable for the purpose intended: the fact that certain gloves allow permeation of irritants and allergens is often overlooked. However, prevention itself may not be sufficient to eradicate ICD. This may be because irritated skin can become hyper-reactive, and the dermatitis may flare with even minimal contact with the eliciting substances. In addition, it is not possible to identify and avoid causative irritants in all cases. Thus, additional therapies to treat ICD are essential in certain cases. Examples of such treatments in clinical practice include cool compresses, moisturizing creams, and PUVA or UV-B phototherapy [59]. In this chapter, we explore available treatments and discuss experimental evidence of their putative mechanisms and benefits.