For most people with atopic dermatitis, management of their skin disease includes years of continuous or intermittent use of topical medications. Counseling on that element of chronic disease management is a crucial part of physician visits for patients with atopic dermatitis. Inevitably, discussions about the long-term safety of patients’ treatment plans are included and these discussions are usually based on little long-term evidence. Randomized clinical trials are often underpowered and too short to detect long-term, rare adverse events. Those clinical discussions became more nuanced with the introduction of the topical calcineurin inhibitors (TCIs) tacrolimus in 2000 and pimecrolimus in 2001, and particularly with the addition of a US Food and Drug Administration black box warning in 2006.1 The addition to the prescribing information warned of potential skin cancer and lymphoma risk associated with TCIs based on the known risk of cancer in patients who have undergone transplantation and then received oral calcineurin inhibitors for immunosuppression, as well as on a number of postmarketing reports of cancers developing after use of TCIs.2