Cancer is the second leading cause of death in most US populations. Unfortunately, ethnic minority status is associated with increased later stage at diagnosis, greater incidence for many cancer sites, differential treatments, greater mortality and morbidity. The government and public health focus on health disparities, evident in several documents including Healthy People 2010, Unequal Treatment and the Nation's Investment in Cancer Research, are spurring interest in research with ethnic minority populations. Research investigating the health-related quality of life (HRQoL) among ethnic minority cancer survivors is new and growing. However, there is a dearth of research that addresses theoretical frameworks in cross cultural research. In conducting research with diverse populations, appropriate theoretical grounding that is responsive to cultural and socioecological contexts must be considered. This paper will discuss the contextual model of HRQoL, a comprehensive framework developed to expand the traditional HRQoL framework to facilitate culturally and socioecologically responsive research. This model may provide a more comprehensive theoretical framework to investigate certain areas of health disparities and risk factors for poor outcomes in HRQoL research with cancer survivors.