Cystic fibrosis (CF) is an inherited autosomal recessive disorder that is associated with chronic multi-organ disease. Recurrent sinopulmonary infections, nutritional abnormalities, and malabsorption serve as a hallmark of most of the morbidity and mortality. Major advances into the understanding of the pathophysiology has led directly to improvement in survival and quality of life. Today, CF is most commonly diagnosed through newborn screening. Newer therapies that serve as CF transmembrane conductance regulator (CFTR) modulators are able to target the basic defect of CF. CFTR mutations are categorized into 5 classes based on the effect of the gene mutation on the CFTR protein function. Best practice is promoted by consensus clinical guidelines from the CF Foundation (CFF). In addition, this centralized Foundation allows for directed and standardized care of the patient that is delivered by multidisciplinary teams of health care providers in an established network of pediatric and adult CF centers accredited and funded by the CFF. Those with CF will continue to benefit from the creation and advancement of novel therapeutic strategies, the continued efforts of clinical research networks, and the support of quality improvement initiatives for treating populations of patients with CF.