BACKGROUND: Research has shown that health system utilization is low for chronic diseases (CDs) other than HIV. We describe the knowledge and perceptions of CDs identified from rural and urban communities in north-west Tanzania and southern Uganda. METHODS: Data were collected through a quantitative population survey, a quantitative health facility survey and focus group discussions (FGDs) and in-depth interviews (IDIs) in subgroups of population survey participants. The main focus of this paper is the findings from the FGDs and IDIs. RESULTS: We conducted 24 FGDs, involving approximately 180 adult participants and IDIs with 116 participants (≥18 years). CDs studied included: asthma/chronic obstructive lung disease (COPD), diabetes, epilepsy, hypertension, cardiac failure and HIV- related disease. The understanding of most chronic conditions involved a combination of biomedical information, gleaned from health facility visits, local people who had suffered from a complaint or knew others who had and beliefs drawn from information shared in the community. The biomedical contribution shows some understanding of the aetiology of a condition and the management of that condition. However, local beliefs for certain conditions (such as epilepsy) suggest that biomedical treatment may be futile and therefore work counter to biomedical prescriptions for management. CONCLUSION: Current perceptions of selected CDs may represent a barrier that prevents people from adopting efficacious health and treatment seeking behaviours. Interventions to improve this situation must include efforts to improve the quality of existing health services, so that people can access relevant, reliable and trustworthy services.