Long-acting antipsychotics constitute a valuable therapeutic option for people suffering from schizophrenia and other psychotic disorders. They are designated for the treatment of psychotic states, mainly in patients with schizophrenia, who require long-term antipsychotic treatment. The most important advantage of long-acting antipsychotics is the fact that they ensure a stable level of antipsychotic medication. Besides, the use of long-acting antipsychotics improves patient's compliance with treatment. Unsatisfactory treatment compliance increases the risk of worsening/relapse and it also increases the risk of patient's re-hospitalization. The improvement of treatment compliance also results in the reduction in family burden caused by the disease. Thus, the second-generation long-acting antipsychotics are of great help in the therapy of people with schizophrenia. The use of a second-generation long-acting antipsychotic agent combines the advantages of the treatment with a long-acting antipsychotic resulting from a more stable drug level with the advantages of the use of an atypical antipsychotic drug: better efficacy against negative and affective symptoms, and better influence on patient's cognitive functioning, but also with the decreased risk of bothersome side-effects, mainly extrapyramidal symptoms. The indications and contra-indications for the use of the second-generation long-acting antipsychotics are presented. The guidelines for the beginning of treatment as well as treatment continuation are also presented. The dosage and the potential drug-drug interactions are discussed with regard to four second-generation long-acting antipsychotics: aripiprazole, olanzapine, paliperidone, and risperidone. The availability of these drugs in Poland is also discussed.