Vascular access dysfunction is a major cause of morbidity in hemodialysis (HD) patients. An upper extremity autogenous arteriovenous fistula (AVF) that preferentially involves the cephalic vein is the access of choice for HD patients, followed by autogenous AVF utilizing the basilic vein and the use of prosthetic arteriovenous grafts (AVGs). Despite these recommendations, central venous catheter (CVC) use is widespread among both incident and prevalent HD patients. Long-term use of CVCs for HD is complicated by a high rate of infection and thrombus-related dysfunction. Catheter locking solutions have been used both prophylactically and therapeutically for catheter thrombosis as well as catheter-related infections, with varying degrees of success. This review aims to address the different catheter locking solutions, their advantages and disadvantages, and new directions in this field.