With recent rapid technological development, the boundaries between work and nonwork roles have been blurred. It is thus of great difficulty to maintain a work-life balance. Among the relationship between work and nonwork roles, interference between work and family has received major attention. The current chapter mainly focuses on the balance between work roles and family roles, and it discusses how work flexibility can help employees to achieve work-life balance, which in turn enhances mental health in the workplace. The chapter begins with a literature review and conceptualization of work-family conflict, work-life balance, and mental health at work in Western and Asian societies. A series of discussions on moderators follow. In particular, a review of family-friendly employment policies and practices in different countries under their cultures is provided to illustrate how the goal of achieving employees’ work-family/work-life balance can be implemented. Lastly, some practical tips are provided to discuss how work flexibility could help maintain employees’ work-life balance and, in turn, facilitate mental health at work.