The abundance of molecular pathways affected by diabetes presents the challenge of understanding complex interactions among the pathways, but also the opportunity of providing multiple and potentially complementary targets for drug development. How do the identified molecular pathways associated with diabetic nephropathy interact within each cell and does this vary for different cell types? Are there undiscovered molecular pathways that contribute to diabetic nephropathy? What is the best way to identify and interrogate these pathways? What protective pathways are present and how do they interact with other pathways? Does nephropathy arise from an imbalance of maladaptive to adaptive responses in animals or patients who are genetically prone to diabetes? What are the relative contributions of hyperglycemia versus impaired insulin and other growth factor signaling in the development of diabetic nephropathy? Why do tubular and glomerular cells initially exposed to the same systemic factors have different pathologies? What is the clinical significance of the identified biochemical changes in the cell induced by diabetes?