Thiazolidinediones (TZD) such as pioglitazone and rosiglitazone are proxisome proliferator-activated receptor gamma (PPARg) agonists and are widely used clinically to treat type 2 diabetes mellitus. Fluid retention still poses a significant limitation to its use. The primary renal process underlying TZD-associated oedema is reduced urinary sodium and water excretion. Experimental evidence suggests that this is mainly related to the effects of PPARg agonists on the distal nephron and collecting duct. We have recently shown that PPARg agonists upregulate sodium and water transport channels in human proximal tubule cells and that Sgk-1 is involved. In this review, we focus on the importance of the proximal tubular cells in TZD-mediated sodium and water uptake.