Thalassemia is a disease with an extensive morbidity profile affecting almost every organ system. Renal involvement, once considered rare, is an underestimated and poorly studied complication that has been on the rise ever since medical advances granted patients longer life spans. Several studies and reports have emerged recently to shed light on the seriousness of this complication, although data is still lacking in terms of pathophysiology, diagnosis, prevention and treatment. In this review, we evaluate and compare renal involvement in the transfusion-dependent and independent variants of β-Thalassemia, highlighting the pathophysiology of kidney damage that involves iron overload, chronic anemia, and iron chelation therapy. An in-depth and focused review of the types of injuries incurred is also presented along with the diagnostic biomarkers accompanying each type of injury. Most research so far has focused on the transfusion-dependent thalassemia population being the group with most renal involvement, however recent reports have shown evidence of comparable, if not worse, involvement of the non-transfusion dependent population, sometimes leading to end-stage renal disease. As such, we try to shed light on distinct renal involvements in NTDT whenever available.