The diagnosis and clinical management of patients with lupus nephritis can be a challenge from a clinicopathologic point of view. Although the majority of patients that are biopsied already have either an established clinical diagnosis or a presumptive diagnosis of systemic lupus erythematosus, determination of the immunomorphologic characteristics, pattern, and distribution of renal involvement is important for clinical management. In a clear subset of these patients with lupus nephritis, electron microscopy plays a pivotal role in accurately characterizing the type of renal involvement and determining the degree of activity, providing useful and objective guides for patients' management. Ultrastructural evaluation can also be crucial in the initial diagnosis of patients with lupus who, at the time of biopsy, lack either diagnostic clinical manifestations and/or serologic markers, and are therefore clinically unsuspected. Electron microscopic evaluation also plays a significant role in the evaluation of renal dysfunction in transplant patients with lupus nephritis, helping to determine whether recurrence of the lupus has occurred in the renal allograft. There are some ultrastructural findings that, although not pathognomonic, in the proper clinico-pathologic context are very suggestive or even diagnostic of lupus nephritis. Correlating light, immunofluorescence, and electron microscopic findings within the clinical context of lupus nephritis cases is crucial for appropriate clinical management. In some of these patients, electron microscopy provides key information that cannot be otherwise obtained.