Background Attitudes toward medication treatment are thought to significantly influence adherence in bipolar disorder (BD) and schizophrenia. However, the actual impact of patients' treatment attitudes on adherence and determinants of attitudes is still uncertain. Methods A longitudinal examination of treatment attitudes and their correlates was conducted among patients with BD and their caregivers compared with those with schizophrenia. Structured assessments of symptom severity, functioning, insight, medication side effects, knowledge of illness, medication adherence, treatment attitudes, and treatment satisfaction were performed among 176 selected patients (106 with BD and 70 with schizophrenia) and their caregivers. Participants were reassessed on these parameters at 3 and 6 months. Results Rates of nonadherence at baseline varied widely between self-reports, clinician ratings, and serum levels. Though symptoms and functioning improved with treatment, overall rates of nonadherence increased in the first 3 months because of early dropouts and remained stable thereafter. However, treatment attitudes and treatment satisfaction remained largely unchanged among patients and caregivers. Both positive and negative attitudes were commonly held and patients' attitudes did not differ between BD and schizophrenia. Patients' attitudes were significantly associated with adherence, insight, knowledge about illness, treatment satisfaction, symptom severity, social disadvantage, and side effects together with caregivers' knowledge, attitudes, and satisfaction. Caregivers of patients with schizophrenia were more knowledgeable and had more positive attitudes than patients. Conclusions Patients' attitudes to medication treatment are associated with adherence over time. They are relatively enduring and mainly associated with insight, knowledge of illness, and treatment satisfaction among patients and their caregivers. These findings could inform psychosocial interventions aiming to improve treatment attitudes and adherence in BD and schizophrenia.