Hospitalization can occur at any age for patients with cystic fibrosis (CF). The leading cause for admission is an acute worsening of signs and symptoms that can be called a pulmonary exacerbation. The reasons for admission are usually the need for intravenous antibiotics and aggressive airway clearance with good nutritional support. Respiratory therapists (RTs) play a key role in the care of CF patients in the out-patient clinics and taking care of the patients while hospitalized. Following the CF pulmonary guidelines, they administer aerosol delivery and airway clearance while also providing education to patients and families. The RT should have the skills to perform and teach all manners of airway clearance and understand the medications and delivery devices that make up a CF treatment. As CF lung disease progresses, so does the chance that these patients may develop complications such as pneumothorax and hemoptysis, which may require different strategies, especially when airway clearance is performed. The RT needs to have the skills that can take the patient from simple oxygen therapy as lung function deteriorates to the point where chronic oxygen or noninvasive ventilation is needed, or to the point where the end-stage patient waits for a lung transplant. An important aspect of the hospitalization is the interaction between the RT and the patient. To give good therapy is to be a great coach. From infection control to following proper nebulizer protocol, to consistency with airway clearance, to education, the CF RT is there for the life of the patient.