Abstract: Burnout is a complex multifaceted concept that affects aspects of caregivers' well-being, the quality of care, and the cost of human services. Research has emphasized multidimensional approaches (individual, interpersonal, and organizational) and has integrated burnout into a larger conceptual framework in order to develop a more comprehensive program of burnout prevention. This review evaluated the findings and overall quality of research that was conducted and published from 1993 to the present from a systematic perspective of informal caregivers, formal caregivers, and human services organizations. Individual factors contributing to caregiver burnout included gender, coping strategies, age, health, restricted activities, ability to cope, self-efficacy, religion, moral distress, sense of coherence, conflicts between personal belief and societal expectation, education, years of experience, and personality. Interpersonal contributing factors included social support, relationship with the care recipient, nature of illness and problem, duration of caregiving, interpretations of information, comparison with others, inequity in the relationship with the care recipients, and nature of the care recipients. Organizational contributing factors included relationship with healthcare professionals, accessibility of professional help, inequity in professional-organizational relations, compassion satisfaction, rotation, content of work, professional characteristics, working setting, and support at work. An overview of theoretical approaches was provided as a foundation for developing burnout prevention. In addition, an overview of research methods on burnout was discussed and provided guidelines of researching burnout prevention. The results indicated that there are advantages of utilizing multidimensional approaches to prevent burnout. However, there is a need to investigate and evaluate burnout preventions; from comprehensive and integrated perspectives. It is recommended to develop a comprehensive, continual, and integrated program on burnout prevention. A program includes a series of courses on assessment, education, skills training, supportive network, and interactive managerial leadership for particular needs among the levels of healthcare system: recipients, family caregivers, healthcare providers, and human service organizations. Furthermore, the open channel of communication that is vertical and horizontal in the healthcare system is crucial to prevent burnout through sharing valuable feedback and suggestions from one another. Hence, a comprehensive, continual, and integrated healthcare system can provide a higher quality of services for each person, family, and society.