The study by Treggiari et al1 published in this issue of the Archives of Pediatrics & Adolescent Medicine represents the latest paradigm shift in the antimicrobial management of people with cystic fibrosis (CF). It is worthwhile to reflect on the sea changes that have occurred in the antimicrobial management of patients with CF during the past 3 decades. During the 1970s and 1980s, clinicians questioned the need for antimicrobial therapy during a pulmonary exacerbation. To assess this, a placebo-controlled trial was conducted in which patients having an exacerbation were randomized to antibiotics vs placebo.2 There was a death in the placebo group. Investigators then asked if clinical improvement during CF exacerbations was the result of antibiotics or the result of the supportive care (eg, rest, bronchodilators, more effective chest physiotherapy) that patients received while hospitalized. To address this question, patients having an exacerbation were hospitalized and randomized to initiation of antibiotics on admission vs 4 days of supportive care prior to the initiation of antibiotics.3 Patients receiving antibiotics on admission did better. The next paradigm shift for the use of antimicrobials in CF occurred when tobramycin inhalation solution was introduced for long-term suppressive therapy in patients chronically infected with Pseudomonas aeruginosa, in efforts to slow the deterioration of lung function.4 While management of exacerbations and long-term suppressive therapy are currently the standard of care for CF, neither of these strategies addresses prevention of disease progression. Thus, the CF community has increasingly practiced early treatment (aka, eradication) of P aeruginosa, ie, initiation of antimicrobial treatment in response to a positive culture for this microorganism, regardless of signs and symptoms of infection. However, the optimal strategy for early treatment and its safety and efficacy were largely unknown and required additional study.