<p>Atopic dermatitis (AD) is a common chronic inflammatory skin condition that significantly impairs patients’ quality of life as a result of intense itching and persistent eczematous lesions. Although AD has a multifaceted etiology—including genetic predisposition, environmental triggers, barrier dysfunction, and dysregulated immune responses—interleukin-4 (IL-4) has a recognized central role in its pathogenesis. This narrative review explores the role of IL-4 in the pathophysiology of AD, its contribution to the atopic march, and the therapeutic impact of IL-4 inhibition. IL-4 plays a critical role in skin barrier dysfunction, dysbiosis, pruritus, and inflammation, all of which contribute to the debilitating symptoms of AD. Moreover, IL-4 is implicated in other atopic conditions, such as asthma, allergic rhinitis, and food allergies, underscoring its role beyond AD and its importance in the atopic march. Recent advances in targeted therapies, particularly IL-4/IL-13 signaling inhibitors, have changed AD management. Dupilumab, an IL-4 receptor antagonist, has demonstrated significant efficacy in reducing AD symptoms and enhancing patient outcomes in both children and adults. In addition to symptomatic relief, suppressing IL-4 signaling may also offer potential for disease modification, altering AD’s progression and possibly preventing the onset of other atopic conditions. This review highlights the crucial role of IL-4 as a therapeutic target in AD. By understanding the role of IL-4 in AD pathogenesis and exploring the therapeutic implications of targeting IL-4 pathways, this work can contribute to guide future research concerning treatment approaches and also emphasize the need for early and targeted interventions to mitigate disease impact and ultimately improve patient quality of life.</p>