Atopic dermatitis (AD) is a common skin disease during infancy, which imposes a considerable burden on patients, their families, and the society, requiring effective treatment options that result in rapid and sustained symptom relief. Additionally, early treatment may prevent the development of atopic comorbidities by restoring the skin barrier. Currently, topical standard-of-care for AD in infants includes emollients and topical corticosteroids (TCS) to treat and reduce the risk of flares. However, only few have been approved for infants and long-term maintenance therapy with TCS is not indicated due to potential local and systemic side effects, including skin atrophy. Accordingly, the recently updated European guidelines for treatment of AD recommend topical calcineurin inhibitors (TCIs) for long-term use, treatment of sensitive skin areas, and for use in the pediatric population. Evidence on the use of TCIs for infants has almost been exclusively collected for pimecrolimus, with >4,000 infants evaluated in clinical trials, consistently confirming that pimecrolimus is a safe and effective treatment for infants with AD. Nevertheless, its use is still restricted in most countries to children above the age of 2 years due to initial and mostly theoretical safety concerns. Based on a careful review of the available evidence of clinical trials, post-marketing surveillance, and epidemiological studies, an Expert Panel of European dermatologists and pediatric allergologists concluded that these safety concerns are no longer valid. Therefore, pimecrolimus offers a safe and effective alternative to TCS in infants aged 3 months and above, and labeling restrictions in this age group are no longer justified.