Background: Tuberculosis (TB) can seriously affect the hematopoietic system, with involvement of both myeloid and lymphoid cell lines as well as plasma components. These hematological changes act as a marker for the diagnosis, prognosis and response to therapy. Methods: We searched PubMed, Scopus, Google Scholar, EMBASE, Cochrane Library and WHO websites from 1950 to May 2021 for papers on the interaction between TB and common and rare hematological manifestation. Results: Hematological reactions in patients with TB are possible in both young and old women and men but seem more frequent in the elderly, and they can be predictors of both diagnosis and worse outcome for TB, regardless of whether it is pulmonary, extra pulmonary or miliary. Even anti-TB therapies can cause hematological adverse events, among which some are serious and rare and can compromise the patient’s recovery pathway to completing treatment. Conclusion: Hematological screening and follow-up, including complete blood count and coagulation, are always necessary both at the diagnosis of TB and during antitubercular treatment in order to monitor hematological parameters. Short therapy regimens for multidrug-resistant TB (MDR-TB) may also be useful for reducing hematological toxicity, especially in contexts where this cannot be monitored. Close monitoring of drug interactions and hematological adverse events is always recommended.