Monoclonal gammopathy of renal significance (MGRS) includes all kidney disorders caused by a monoclonal protein (M-protein) secreted by a small plasma cell clone or other B-cell clones in patients who do not meet the diagnostic criteria for multiple myeloma or other B-cell malignancies. The underlying disorder in patients with MGRS is generally consistent with monoclonal gammopathy of undetermined significance (MGUS). MGRS-associated kidney disorders are various and the list is still expanding. The kidney disorders can manifest as glomerular diseases, tubulopathies, and vascular involvement with varying clinical presentations. Diagnosis is often challenging because of the wide spectrum of MGRS, and it is difficult to establish a pathogenic link between the presence of the M-protein or serum free light chains and kidney diseases; further complicating accurate diagnosis is the high incidence of MGUS and/or kidney disorders, independent of MGRS, in elderly patients. However, MGRS can significantly impair kidney function. Because treatment can stop and also reverse kidney disease, early recognition is of great importance. A combined haematologic and nephrologic approach is crucial to establish the causative role of the M-protein in the pathogenesis of kidney disease. Clone-directed therapy, which may include autologous stem cell transplantation in eligible patients, often results in improved outcomes. In this review, we discuss the histopathologic classification of MGRS lesions, provide a renal and haematologic diagnostic workup, discuss treatment options for MGRS, and introduce a Benelux MGRS Working Group.