This prospective longitudinal 15-year multifollow-up research studied whether unmedicated patients with schizophrenia can function as well as schizophrenia patients on antipsychotic medications. If so, can differences in premorbid characteristics and personality factors account for this? One hundred and forty-five patients, including 64 with schizophrenia, were evaluated on premorbid variables, assessed prospectively at index hospitalization, and then followed up 5 times over 15 years. At each follow-up, patients were compared on symptoms and global outcome. A larger percent of schizophrenia patients not on antipsychotics showed periods of recovery and better global functioning (p < .001). The longitudinal data identify a subgroup of schizophrenia patients who do not immediately relapse while off antipsychotics and experience intervals of recovery. Their more favorable outcome is associated with internal characteristics of the patients, including better premorbid developmental achievements, favorable personality and attitudinal approaches, less vulnerability, greater resilience, and favorable prognostic factors. The current longitudinal data suggest not all schizophrenia patients need to use antipsychotic medications continuously throughout their lives.