Long-acting injectable antipsychotics (LAI AP) were mainly developed with the intention to improve adherence to treatment in schizophrenia patients and to reduce the high rates of relapses and re-hospitalizations due to treatment discontinuation. Several studies comparing LAI AP with oral antipsychotics in schizophrenia have been performed, in which RCTs (considered to be the 'gold standard' for clinical trial design) generally show no benefit for LAI AP over oral drugs, whereas observational studies do. The more pragmatic the study design, the more likely it is to show a benefit for LAI AP versus oral therapy. Seeing that the percentage of patients who are currently being treated with LAI AP is far from the percentage of non-adherent patients, it can be argued that LAI AP are significantly underused. LAI AP formulations of antipsychotics have traditionally been used for those patients with schizophrenia with the most severe symptoms, poorest compliance, most hospitalizations, and poorest outcomes, namely at the latter stages of their illness. However, an increasing number of authors suggest that early-phase patients may have the most to gain from LAI AP, at a time when their disorder is most treatable and when avoidance of recurrences and re-hospitalizations may lead to the greatest benefits. To prove the advantage of LAI AP versus oral antipsychotics, there has been an evolution to a new type of clinical trial design that combines some of the best features of both naturalistic "real life" studies and RCTs, namely pragmatic RCT. Currently, there is an ongoing trial in Israel and European countries (the EULAST study) that is an example of this kind of "new" clinical trial design. EULAST is a pragmatic randomized open label cohort study that includes a naturalistic type of follow-up among schizophrenic patients who are early in the disease course. Hopefully, it will dispel doubts concerning the advantages of LAI AP versus oral antipsychotics and will help clinicians to optimize patient's outcomes.