Interest in sorbents for chronic dialysis treatment has revived much attention due to their potential to remove challenging substances and regenerate dialysate, essential for portable or wearable treatments and reducing water consumption. Sorbent-enhanced dialysis with synthetic polymers has shown reduced inflammation and improved survival in smaller studies. Incorporating sorbents into dialysis membranes could simplify dual therapy but requires in vivo testing. Current dialysate regeneration uses urease, zirconium-based sorbents, and activated charcoal, with challenges like sodium release and CO2 from urea hydrolysis, despite short-term trials. A direct urea sorbent would be beneficial for broader applications. Crystalline α- and γ-zirconium phosphates, synthesized via a mechanochemistry-assisted protocol, showed high uptake capacities for NH4⁺ and K⁺ ions, crucial for renal sorbent dialysis systems. The resurgence of home hemodialysis has renewed interest in cost-effective, portable, and efficient systems, with sorbents playing a key role. Sorbent dialysate regeneration involves recirculating dialyzer effluent across a sorbent column to ensure ultra-pure water for reuse. Technological advancements focus on sorbent-based dialysate circuitry, aiming for miniaturization and flexibility, with the modern sorbent hemodialyzer showing promise in clinical settings.