Schizophrenia is a chronic, severe and recurrent brain disorder that requires continuous, long-term treatment with antipsychotic medication to minimize relapse and provide clinical benefit to patients. For patients with schizophrenia, non-adherence to medication is a major risk factor for relapse and re-hospitalization. Long-acting injectable formulations of second-generation antipsychotics (SGAs-LAIs) provide constant medication delivery and the potential for improved adherence. Currently, three drugs are available for the treatment of schizophrenia, risperidone longacting injectable, olanzapine pamoate and paliperidone palmitate. Several studies have also demonstrated efficacy and safety of such drugs in patients with acute schizophrenia. In the present paper the literature on LAI atypical antipsychotics will be reviewed and practical advice will be given concerning the use of these drugs in the clinical practice.