The primary cause of morbidity and mortality in children with cystic fibrosis (CF) is the progression of obstructive lung disease secondary to chronic endobronchial infection, mainly caused by Pseudomonas aeruginosa (Pa). Initial Pa isolates are typically non-mucoid, usually susceptible to most anti-pseudomonal antibiotics, and potentially amenable to eradication. Preliminary studies of early intervention suggest a "window of opportunity" with anti-pseudomonal antibiotics to eradicate Pa from upper and lower airways. Several large trials in young children with CF are currently ongoing with the goals of (1) investigating if early intervention at the time of initial Pa acquisition is effective and safe and (2) identifying the least invasive and safest treatment regimen to achieve both microbiologic and clinical benefits.