Restless Leg Syndrome (RLS), or Willis-Ekbom disease (WED), is an irresistible urge to move the legs, predominantly while resting, sitting, or sleeping, which disrupts sleep and impairs quality of life. RLS can occur secondary to uremia in chronic kidney disease (CKD) patients due to inadequate hemodialysis. Early diagnosis is essential to prevent muscular atrophy and to improve the quality of life of RLS patients, especially those with end-stage renal disease (ESRD). Cardiac mortality high in uremic RLS patients due to associated discomfort and lowering the duration of hemodialysis treatment. This review focuses on and discusses the diagnosis, treatment, and associated comorbid conditions of uremic RLS. Though the exact pathophysiology is unknown, altered transferrin expression in the choroid plexus, increased glutamate levels in the thalamus, decreased opioid receptors, dopamine system dysfunction, calcium/phosphate imbalance, and single nucleotide polymorphisms in the BTBD9 and MEIS1 genes are a few nonconfirmatory pathophysiological concepts for uremic RLS. Nonpharmacological options include lowering the temperature of dialysate by 1 degree C and home-based therapies like massages, warm/cold baths, and aerobic exercises. Pharmacological therapy like dopamine agonists ropinirole and pramipexole reduces the symptoms effectively. However, surgical options like parathyroidectomy and renal transplantation are stated as the best treatment options in patients suffering from uremic RLS.