At least 25% of patients with chronic kidney disease (CKD), and between 50% to 86% of patients with CKD on dialysis suffer from CKD-associated pruritus (CKD-aP). The itch can substantially interfere with sleep and quality of life and has been linked with depression, fatigue, and isolation. There are at least 4 pathways that have been hypothesized as possible etiologies of CKD-aP, leading to a wide range of potential therapeutic strategies for the itch. Difelikefalin is the first agent FDA-approved specifically for the treatment of moderate-to-severe pruritus in CKD patients undergoing dialysis; it is a peripheral kappa-opioid receptor agonist that targets the opioid dysregulation theory. It is imperative that all clinicians involved in the care of patients with CKD routinely inquire about pruritus and adequately treat their patients for CKD-aP. This case-based program will apply the foundational information presented in the first program of this 2-part series to real-world patients.