Objective: To review the efficacy and safety of crisaborole and its place in therapy for the management of mild to moderate atopic dermatitis (AD). Data Sources: A literature search of PubMed (data inception to February 2019) was performed using the search terms crisaborole and atopic dermatitis. Supplementary sources included the Journal of the American Academy of Dermatology Guidelines of Care for the Management of Atopic Dermatitis, clinicaltrials.gov data, manufacturer prescribing information, and article bibliographies. Study Selection and Data Extraction: Relevant English-language studies and those conducted in humans were considered and reviewed. Abstracts from clinical trials and drug reviews were reviewed. Phases I, II, III, and long-term safety studies were included. Data Synthesis: Data from multiple clinical trials have demonstrated the effectiveness and safety of crisaborole topical ointment. Patients treated with crisaborole experienced improvement in AD symptoms based on improvement in the Investigator’s Static Global Assessment and the AD Severity Index scores. Crisaborole has a limited adverse event profile and low systemic absorption. Relevance to Patient Care and Clinical Practice: Crisaborole is the first topical phosphodiesterase 4 inhibitor indicated for the treatment of mild to moderate AD. Its place in therapy is along with topical calcineurin inhibitors as a second-line option for patients who are recalcitrant to or unable to use topical corticosteroids. Conclusions: Crisaborole is a safe and efficacious second-line option for the treatment of mild to moderate AD in patients 2 years of age and older.