Despite the considerable efforts made to increase the prevalence of autogenous fistula in patients on hemodialysis, tunneled cuffed catheters are still an important access modality and used in a high percentage of the hemodialysis population. However, because of the conundrum posed by tunneled cuffed catheters, patients can develop a multitude of complications, including thrombosis, infections, formation of a fibrin sheath, and central vein stenosis, resulting in increased morbidity and mortality as well as placing a heavy burden on the healthcare system. However, with an increasing number of studies now focusing on how to manage these catheter-related complications, there has been less translational research on the pathology of these complications. This review of the most recent literature provides an update on the pathological aspects of catheter-related complications, highlighting what we need to know and what is yet to be discovered. The future research strategies and innovations needed to prevent these complications are also addressed.