There is a resurgence in clinical adoption of home hemodialysis globally driven by several demonstrated clinical and economic advantages. Yet, the overall adoption of home hemodialysis remains under-represented in most countries. The practicality of managing ESKD with home hemodialysis is a common concern among practicing nephrologists in the United States. The primary objective of this invited feature is to deliver a practical guide to managing ESKD with home hemodialysis. We have included common clinical scenarios, clinical and infrastructure management problems, and approaches to the day-to-day management of patients undergoing home hemodialysis.