Cystic Fibrosis is a multi-systemic disease of impaired sodium and chloride transport across epithelial surfaces. Cystic fibrosis is one of the most common autosomal recessive diseases amongst Caucasian children. However, recent epidemiologic studies suggest that the disease in Hispanic, African American, and Asian American populations may be more common than previously recognized. The phenotypic expression is characterized by the constellation of pulmonary, pancreatic, hepatobiliary, and gastrointestinal dysfunction. Progressive obstructive lung disease is the hallmark of cystic fibrosis, and end-stage respiratory failure is the primary cause of morbidity and mortality. The most significant advance in the care has been the development of Cystic Fibrosis modulators, a class of drugs that restore cystic fibrosis transmembrane conductance regulator folding, intracellular processing, or function. Improved diagnostic abilities, a multidisciplinary approach to medical management, and the use of cystic fibrosis modulators have led to improvement in the quality of life and life expectancy. These patients undergo range of procedures such as nasal polypectomy, placement of gastrostomy tubes, vascular access device placement, transbronchial lung biopsies, and other thoracic surgeries. The anesthetic care of children with advanced cystic fibrosis disease is complex. Preoperative optimization can help improve postoperative outcomes. Strategies for pain control should rely on non-opiate, multimodal adjuncts, and regional or neuraxial techniques. Unfortunately for some children, a progressive respiratory disease often leads to end-stage respiratory failure and lung transplant surgery remains the only viable treatment option. Widespread use of lung transplant surgery as a treatment option is severely constraint by donor organ availability. Primary graft dysfunction is the most common cause of early death and can be seen within 48 hours of surgery. Median long-term survival after lung transplant remains modest. Chronic lung allograft dysfunction, opportunistic infections, and post-transplant lymphoproliferative disorder are the most common causes of morbidity and mortality amongst long-term survivors.