Chronic kidney disease (CKD) is highly prevalent in the United States. Patients with stage IV–V CKD or end-stage renal disease (ESRD) require initiation of renal replacement therapy (RRT). A high index of suspicion and careful patient monitoring are important obligations of the primary care physician, followed by referral to medical and surgical specialists. Kidney transplantation remains the best option with respect to survival and quality of life but has an extensive waiting list. Therefore, most patients will need to initiate RRT via hemodialysis (HD) or peritoneal dialysis (PD). While the vast majority choose HD, PD has several advantages in cost, patient satisfaction, and quality of life and should be considered in the appropriate patient population. No matter which mode is chosen, reliable access is paramount for the management of ESRD patients. For HD, a surgically created arteriovenous fistula is the preferred option, while PD requires an intra-abdominal PD catheter to be placed and maintained. Care of CKD and ESRD patients requires close multidisciplinary collaboration between patients, primary care physicians, nephrologists, and surgeons.