Atopic dermatitis (AD) is a common, heterogeneous, inflammatory skin disorder characterized by chronic or relapsing eczematous lesions with intense pruritus and discomfort. Affected patients often experience significant impairment in their quality of life, and the treatment of moderate-to-severe AD forms remains challenging. In the past few decades, increasing knowledge on the AD pathogenesis has driven the development of novel targeted therapies. Interleukin (IL)-13 plays a central and pleiotropic role in AD pathogenesis, contributing directly or indirectly to epidermal barrier disfunction, type-2 inflammation, dysbiosis, fibrosis, and itch response. For this reason, agents selectively targeting IL-13, such as lebrikizumab, emerged as a potential therapy for AD. This article reviews the current evidence about lebrikizumab in the management of AD. The phase II and phase III trials seem to corroborate efficacy of lebrikizumab in the treatment of moderate-to-severe AD, as shown by significant improvement of Eczema Area and Severity Index, body surface area, and pruritus scores. Also, lebrikizumab demonstrated favorable safety and tolerability profiles, with the majority of patients experiencing no significant adverse events. Lebrikizumab seems to be a promising emerging targeted biological agent for patients with moderate-to-severe AD. More data on the long-term efficacy and safety, head-to-head comparisons with other agents, and real-world evidence will help to clarify its place in therapy in AD.