Irritant contact dermatitis (ICD) is the clinical result of an acute or chronic skin inflammation caused by contact with an external chemical, biologic, or physical agent with irritant properties. It occurs when the irritating factor overcomes the skin’s defense and repair capabilities, initiating an inflammatory cascade with release of proinflammatory cytokines from the skin cells. ICD does not constitute a separate clinical entity but rather a complex biological syndrome integrating a wide spectrum of conditions with diverse morphologies and mechanisms. Making a correct diagnosis and identifying the causative agent is of utmost importance for the institution of appropriate therapeutic and preventive measures. The diagnosis of ICD is largely a diagnosis of exclusion, as there are no specific diagnostic tests, so other forms of dermatitis, especially allergic contact dermatitis (ACD), must be ruled out. However, ICD shows similarities with ACD and even endogenous eczema in many aspects, such as clinical characteristics, histopathology, and immunohistochemistry, and no pathognomonic clinical signs and symptoms can make an unequivocal diagnosis. We will discuss the importance of an oriented clinical history and clinical examination, the assessment of exposure, and the clinical clues that may provide guidance. The basis for the diagnosis of ICD is established by relating the clinical characteristics and the time course of the dermatitis to the frequency and intensity of the putative irritant exposure. In addition, the crucial component for a correct diagnosis of ICD is a negative result in a comprehensive and rigorous patch testing.