The classification of kidney disease based on pathogenesis, in addition to clinical and kidney biopsy features, represents a major challenge in nephrology. Identification of the M-type phospholipase A2 receptor (PLA2R) as the likely target antigen for the majority of patients with membranous nephropathy and APOL1 risk alleles as major risk factors for kidney disease in patients of African ancestry represent important strides toward this goal. A number of studies have demonstrated that genetic testing using whole-exome sequencing (WES) detects monogenic causes of kidney disease in a significant number of patients with predefined clinical phenotypes and/or strong family histories of kidney disease (Table 1).