Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects up to 25% of children and 10% of adults. The skin of patients with moderate to severe AD is characterized by significant barrier disruption and T helper 2 (Th2)-driven inflammation, which are thought to play a significant role in the pathogenesis of AD. Current management of AD is aimed at suppressing the inflammatory response and restoring the barrier function of the skin, reducing exacerbations, and preventing secondary skin infections. Combinations of treatment strategies are used to alleviate the symptoms of the disease; however, resolution is often temporary, and long-term usage of some of the medications for AD can be associated with significant side effects. Antibody therapies previously approved for other inflammatory diseases have been evaluated in patients with AD. Unfortunately, they have often failed to result in significant clinical improvement. Monoclonal antibodies and novel small molecules currently in development may provide more consistent benefit to patients with AD by specifically targeting the immune and molecular pathways important for the pathogenesis of AD. Here we review the state-of-the-art therapeutics targeting the Th2 axis in AD.