The Janus kinases (JAK) are a group of molecules, composed of JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2), which are key components within the JAK–signal transducers and activators of transcription pathway, where cytokine receptor signaling takes place. These molecules play a foundational role in the underlying pathogenesis of multiple immune-related conditions such as atopic dermatitis (AD), rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, and others. Thus far, JAK inhibitors for inflammatory conditions have only been marketed for the treatment of rheumatoid arthritis and psoriatic arthritis, but ongoing phase II and phase III clinical trials for other immune-mediated diseases, such as AD, have also shown promising results. This review summarizes the clinical data available from various trials and reports on the safety and efficacy of abrocitinib, baricitinib, and upadacitinib, the three oral systemic JAK inhibitors used in the treatment of AD. The safety and efficacy of JAK inhibitors for the treatment of AD are emerging in the literature. It is important that dermatologists are aware of any potential adverse events or risks associated with the use of JAK inhibitors in order to promote a higher standard of treatment and quality of living.