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ABSTRACT Introduction Linezolid can cause serious adverse effects including thrombocytopenia and anemia. Here, we focus specifically on linezolid-related hematological toxicity in adult patients requiring prolonged drug treatment. Areas covered We review the available evidence on the likelihood of hematological toxicity in adult patients treated with linezolid, with a focus on the main risk factors and strategies to prevent this adverse event. A MEDLINE PubMed search for articles published from January 2000 to May 2022 was completed matching the terms linezolid, hematology, hematological toxicity, anemia, and thrombocytopenia. Moreover, additional studies were identified from the reference lists of retrieved articles. Expert opinion Thrombocytopenia is the major concern with administration of linezolid for Gram-positive infections, whereas anemia is more common in patients with tuberculosis. The important clinical risk factors for the development of linezolid-related thrombocytopenia are aging, renal dysfunction, low baseline platelet count, duration of treatment, and linezolid plasma trough concentrations >8 mg/L. Patients receiving linezolid for extended periods of time or patient populations with increased risk of altered drug pharmacokinetics would benefit from therapeutic drug monitoring or from the availability of toxico-dynamic predictive models to optimize linezolid dosing.