Everolimus – an inhibitor of the mTOR pathway – has an established role in the treatment of advanced renal cell cancer (RCC), neuroendocrine tumors of pancreatic origin (pNET) and renal angiomyolipoma and tuberous sclerosis complex (TSC) . Moreover, everolimus, combined with the aromatase inhibitor exemestane, has been approved for the treatment of postmenopausal patients with advanced breast cancer positive for the hormone receptors (HR+) and negative for the HER2– recurring or progressing after treatment with nonsteroidal aromatase inhibitors . Everolimus is administered orally, at a dose of 10 mg/day continuously. At this dosage, no evidence of cumulative toxicity has been reported in clinical trials over a period of 20–52 weeks . The optimal use of everolimus in breast cancer relies upon adequate management, in order to maximize treatment exposure and, therefore, optimize the clinical outcomes. However, since everolimus has only recently entered the breast cancer arena, physicians may be unfamiliar with its adverse event profile and their management. Given the low threshold for change in therapy in the breast cancer setting – which can be likely attributed to the availability of multiple treatment options – we believe that information on the correct management of everolimus-based treatment in breast cancer patients is important to improve outcomes. This editorial discusses some open issues related to the clinical management of breast cancer patients receiving everolimus.