The introduction of quantitative assays for serum free light chains (FLC) has changed the approach to screening for monoclonal gammopathies. Recent guidelines from the International Myeloma Working Group have recommended the use of serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE) and FLC as the screening panel unless primary amyloidosis (AL) is suspected. If screening for AL, then urine IFE should also be performed. We discuss the background for these recommendations as well as data showing that SPEP and FLC alone may provide a simplified screening panel for detecting multiple myeloma (MM) and Waldenström's macroglobulinaemia (WM) with little loss of diagnostic sensitivity. If AL is suspected, we support the recommendation to include serum and urine IFE. The selective use of serum and urine IFE requires that clinical judgment be integral to ordering screening panels for detection of monoclonal gammopathies.