Exocrine pancreatic insufficiency (EPI) is highly prevalent among individuals with cystic fibrosis (CF). Individuals diagnosed with EPI are often labeled as having “pancreas insufficient cystic fibrosis (PI-CF)” while those with normal exocrine function are labeled as “pancreas sufficient CF (PS-CF).” This diagnosis of EPI relies on clinical and laboratory features and management involves consumption of pancreas enzyme replacement therapy. In this review, we discuss the nuances of diagnosis and management of EPI in CF. We also present emerging evidence on the effects of CFTR modulating agents on the management of EPI, and speculate that these medications may lead to greater heterogeneity in management of EPI in CF moving forward.