Summarize and synthesize the current literature regarding long-acting injectable paliperidone palmitate for the treatment of schizophrenia. A literature search of PubMed, Embase, and Web of Science was conducted in February 2016, using the following search terms in varying permutations: schizophrenia; antipsychotic medication; long-acting injectable; paliperidone palmitate; 3-monthly injectable. Once-monthly injectable paliperidone palmitate (PDP) has demonstrated comparable efficacy as 1st-generation long-acting injectable antipsychotics (LAIAs) in reducing disease severity and re-hospitalizations in schizophrenic patients. However, PDP leads to significantly less extrapyramidal symptoms than these older medications indicating a superior safety profile. Compared to oral 2nd-generation antipsychotics, PDP has shown less incidence of disease relapse related to medication non-compliance, particularly in real world populations. It also showed a similar safety profile as oral 2nd-generation antipsychotics, but with greater incidence of mild injection-site pain. A novel 3-monthly formulation of PDP has shown similar safety and efficacy as once-monthly PDP compared to placebo. Overall, both 1-month and 3-month formulations of PDP are safe and effective in the treatment of schizophrenia and schizoaffective disorder. They may be most effective in patients with prior failed treatment of oral antipsychotics or other LAIAs, in patients with a history of medication noncompliance, or in patients with an individual preference for less frequent dosing.