Cystic fibrosis (CF) is the most common genetic disorder in Caucasian individuals, with an incidence of 1/2,500-3,500 live births. When CF was first described in 1938, most children died in infancy. Currently, the average lifespan is 28-47.7 years. Although new breakthroughs have occurred, CF is still incurable. Both early diagnosis and treatment by multidisciplinary teams are essential to optimize short- and long-term outcomes. It is imperative for neonatal clinicians to keep up to date on the most current research, treatment, and management of CF to provide the best outcomes. This article offers clinicians an updated review of the pathophysiology and clinical manifestations of CF, as well as current evidence-based diagnostics and treatment regimens.