Diabetic nephropathy is a complex disease, caused by both environmental and genetic factors. As in most complex diseases, genetic association studies in diabetic nephropathy showed inconsistent results. In retrospect, studies with small sample sizes, given what are now known to be small odds ratios, were partially responsible for this poor replication record. Furthermore, the low prior probability in complex genetics and multiple testing played a role. Results become more consistent when one only considers those that were replicated. In a large meta-analysis study including only replicated associated genetic variants, 24 genetic variants in 16 genes were found to be associated with diabetic nephropathy. These genetic variants may provide novel biological insight. In particular, rare variants with a large effect found by hypothesis-free approaches (genome-wide association scans, next-generation sequencing) may open new avenues of discovery.