Mexican-Americans carry a high burden of type 2 diabetes and are disproportionately affected by diabetes related mortality and morbidity. Poor adherence to medication is an important barrier to achieving metabolic control and contributes to adverse health outcomes and health disparities. Little is known about barriers and facilitators to medication adherence among Mexican-Americans with diabetes. This is a qualitative study of semi-structured interviews with a sample of 27 adults (25 Mexican-Americans and 2 Latinos of other origin) with self-reported type 2 diabetes who were recruited as part of a church-based, randomized controlled trial for diabetes self-management education in a low-income, immigrant neighborhood of Chicago. Face-to-face, in-depth interviews were conducted (one in English and 26 in Spanish), audio-recorded, transcribed verbatim, and professionally translated. Systematic qualitative methods were used to analyze interviews. All 27 participants were Latino, and 25 were of Mexican descent. Participants' mean age was 57 years, 81% were female, 69% had an annual income less than $20,000 and 48% had no health insurance. Mean A1C level was 8.6% and mean systolic blood pressure was 125 mmHg. The majority of participants (85%) reported using oral diabetes medication and 35% reported taking insulin. 76% reported being affiliated with one of the two partnering catholic churches based in the South Lawndale neighborhood of Chicago, also known as Little Village. Concerns regarding effectiveness and negative impact of diabetes medication were prevalent and expressed by 13 (48%) of 27 participants. Dissatisfaction with ineffective provider communication and not being able to pay for medication were other important barriers to adherence and were expressed by 7% and 11% of participants, respectively. Family support, for example, family members assisting in organizing medications in boxes and reminding participants to take them, was reported by 15% of participants and emerged as an important facilitator to medication adherence. There is a gap in research on factors influencing adherence to diabetes medication among Mexican-Americans. Our study suggests that concerns regarding negative impact of diabetes medication and concerns regarding effectiveness are prevalent barriers to adherence. These barriers can be addressed through educational efforts targeting patients and clinicians by specifically including content on beliefs that lead to poor adherence in diabetes self-management interventions for patients and continuing medical education for providers and by developing interventions that engage family members as a support system for medication adherence.