Comprehensive psychiatric rehabilitation programs in Latin America have been designed across several countries in the region without yet achieving full implementation. Facing an increasing burden of disease due to mental disorders, including alcohol and substance use disorders, the region has responded unevenly to the challenge. Moreover, low priority for mental health in national policies and insufficient funding for mental health services are common barriers for the much-needed mental health services reforms. Reestablishing a primary care community-based model of care has been a shared aspiration for most countries during the last two decades. Comprehensive models of psychiatric rehabilitation developed predominantly in high-income countries need to be culturally adapted to local contexts, while strengthening health systems research will provide evidence on the efficiency of locally designed interventions and on the critical milestones to succeed in the scaling up strategies. Increasing participation of patients and their families in the mental health delivery system is another key factor in order to ensure comprehensive patient-centred psychosocial rehabilitation programs in Latin America.