Therapeutic drug monitoring (TDM) studies are generally focused on keeping chronic drug exposure to minimal effective blood levels to better control compliance and to avoid side effects. The usefulness of TDM applied to new generation antipsychotics (NGAs) is still under discussion, especially in clinical settings, even though there are evidences in literature that TDM can improve efficacy, especially in non-responders or in patients developing side effects with sub-therapeutic doses. In addition, drug plasma level determinations can be of some utility in medical legal problems. Optimal plasma level ranges are proposed for clozapine, risperidone, paliperidone and olanzapine. The available data on quetiapine, amisulpride, asenapine, iloperidone and lurasidone provide only limited information, while there is no direct evidence concerning ziprasidone, aripiprazole, brexpiprazole, cariprazine and lumateperone.