IgA nephropathy is the most common primary glomerulonephritis worldwide, and an important cause of kidney failure, as 20-40% of patients progress to renal replacement therapy 20-30 years after diagnosis. Its clinical presentation ranges from isolated microscopic hematuria to nephrotic syndrome, and even to a rapidly progressive course. Ethnicity and epigenetics play a key role in its clinical aggressiveness. Selection of patients at risk needing immunosuppressive treatment is a challenge for the nephrologist. Some active and chronic kidney lesions detected on kidney biopsy have been demonstrated to have prognostic value according to the Oxford Classification of IgA nephropathy, later validated by numerous studies. However, KDIGO 2021 guidelines still consider persistent proteinuria > 1 g/24 h to be the most relevant risk factor for the progression of IgA nephropathy and the only one requiring immunosuppressive treatment. KDIGO guidelines have proposed a therapeutic algorithm, but many patients present peculiar characteristics that are not addressed by the current guidelines, pointing to the need for alternative approaches. In these cases, a tailored approach to each patient should be followed in which clinical, histological, laboratory, social and ethical aspects must be considered. In this manuscript we present three cases of IgA nephropathy from different countries, highlighting many of the aspects encountered in clinical practice that illustrate an individualized approach to the treatment of these patients.© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.