Mammalian target of rapamycin (mTOR) inhibitors are currently considered an alternative immunosuppressive treatment that can prevent the nephrotoxicity, viral infections and malignancies that are associated with calcineurin inhibitor-based immunosuppressive regimens. However, the side effects of mTOR-inhibitor-based regimens lead to frequent treatment discontinuations, and not all patients seem to have the same benefits from conversion to mTOR inhibitors. This review focuses on long-term results of trials that have assessed early and late conversion to sirolimus or everolimus. The renal benefit of late conversion (≥1 year post transplantation) is limited, except in patients with good renal function and without proteinuria. Early conversion to mTOR inhibitors in the first 6 months, in combination with mycophenolate mofetil, could be an appropriate strategy for maintenance therapy in renal transplant recipients with a low immunological risk after careful screening at the time of conversion. Good renal function (glomerular filtration rate >40 ml/ minute), weak proteinuria (<1 g/day), an absence of previous acute rejection and subclinical rejection, and appearance of donor-specific anti-human leukocyte antigen antibodies appear to be the most important criteria in identifying patients for whom conversion to an mTOR inhibitor may improve renal function at 5 years.