This article explores mixed-method approaches with an illness called myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Qualitative and Quantitative data were used to investigate the epidemiology of this illness, as well as explore attributions based on the name of the illness, and finally treatment approaches. In each of the domains within the ME and CFS research reviewed, our analyses were richer and our findings ultimately more impactful when we integrated qualitative and quantitative research methods. The use of a multiphase mixed-methods research program provided our team unique vantage points for better understanding social and community issues involving this controversial chronic illness. Furthermore, this approach allowed us to implement the insights gained through an advocacy lens to change policy, recommend and evaluate treatments, and amplify voices within the patient population. In this way, we believe that the practice of methodological pluralism is especially applicable and effective to the study of chronic illness, and believe that other investigators will benefit from the use of these approaches with similar disenfranchised and unfairly treated populations.