Diabetes mellitus is rapidly becoming a global health issue that may overtake cancer during the next two decades as it covertly affects multiple organ systems that goes undiagnosed long after the onset. A number of complications are associated with poorly controlled hyperglycemia. Diabetic nephropathy is one of the most common complications of diabetes mellitus. Other than angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blocker (ARB) there is not much in the armamentarium with which to treat patients with overt diabetic nephropathy. Research points towards a multifactorial etiology and complex interplay of several pathogenic pathways that can contribute to the declining kidney function in diabetes. Patients with diabetic nephropathy (and with any chronic kidney disease) eventually develop kidney fibrosis. Despite the financial and labor investment spent on determining the basic mechanism of fibrosis, not much progress has been made in terms of therapeutic targets available to us today. This may be in part due to paucity in the experimental animal models available. However, there now seems to be a concerted effort from several pharmaceutical companies to develop a drug that would halt/delay the process of fibrosis, if not reverse it. This review discusses the current state of research in the field while staying within the context of diabetic nephropathy.