Like many countries in Sub-Saharan Africa, Hepatitis B virus (HBV) is highly prevalent in Ghana. Using qualitative methods, this paper draws from the political ecology of health theoretical framework to examine perceptions and understandings of HBV in the Upper West Region of Ghana. The findings reveal that extremely low levels of knowledge and pervasive lay misconceptions about the disease within this geographic context are shaped by large scale structural influences. Furthermore, in this context there is essentially no access to HBV immunizations, testing or treatment services which reinforces potential routes for the spread of HBV. An explosive spread of HBV is brewing with the potential to diffuse across space and time while, within the institutional contexts, it is the HIV epidemic that is largely consuming both policy attention and intervention.