In 2012, the Piedmontese Clinical Nephrology Group retrospectively analyzed a cohort of patients diagnosed with focal and segmental glomerulosclerosis (FSGS) in Piedmont and the Aosta Valley, with a special focus on frequency of disease, choice and duration of treatment at disease onset and during relapses. Seventeen centers participated. The total number of FSGS cases was 467: 148 were diagnosed between 1991 and 2000 and 319 between 2001 and 2010, corresponding to a 127% increase in the latter decade. First-line treatment in 9 centers was full-dose corticosteroid (CS) for 4 months with 8 centers using CS for 2-3 months. One center used additional iv CS pulse treatment. Dosage tapering lasted 3-9 months; in one center dose tapering lasted for less than 3 months. During first relapse, 10 centers used CS as drug of choice, 4 centers CS and cyclosporin (CyA), 3 centers CS and cyclophosphamide (CyF), with one center using chlorambucil instead of CyF. In 2 centers CyA or CyF were each considered appropriate and employed on an individual basis. Only one center considered mycophenolate (MMF) as a treatment option. If multiple relapses occurred, 14 centers chose CyA as drug of choice, 2 centers CyF (in association with low-dose CS) and 1 center did not report any multiple relapses. Eight centers proposed a variation in therapeutic approach: MMF (5), Rituximab (3), Tacrolimus (1), CyF (1), ACTH (1). If CS dependence occurred, the maximum dose allowed was considered to be 15 mg/day in 2 centers, 12.5 mg/die in 4 centers, 10 mg/die in 4 more centers, 7.5 mg/die in 1 center, and 5 mg/die in a further one. Three centers did not refer any experience with CS dependence. Only 4 centers had direct experience with MMF and maintained treatment for about 3 years. In relapsing cases with a good response to CyA, the drug was discontinued after 5 years in 2 centers, after 3 years in 2 centers, 2 years in 4 centers, 1 year and a half in 2 centers, and 1 year in 3 centers. CyA was used as a long-term treatment in 3 centers. In conclusion, Piedmontese nephrologists followed K-DOQI guidelines in typical cases of FSGS. When the disease presents with an atypical course nephrologists' decisions appeared to be influenced by their experience with atypical drugs, such as MMF and Rituximab. Studies with other drugs are needed to improve the prognosis of forms of FSGS resistant to current treatments, which have remained virtually unchanged since the 1970s.