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Many people living with HIV in Ghana make use of spiritual therapy, however complex. This paper describes the complexities of these therapies in the context of increasing access to antiretroviral (ARV) drugs and high levels of HIV stigma. The study took place in Kumasi and Offinso, both in the Ashanti Region of Ghana (the most populated region, with around 4.5 million people), and is the result of 15 months of anthropological and ethnographic research utilising observations and in-depth interviews with 48 HIV-positive persons, their families, and other significant people in the lives. The article describes the participants' experience of their HIV infection as a 'spiritual challenge,' which thereby formulated a personal need to 'heal body and soul.' The findings illustrate how crossing religious and denominational boundaries is an important element in people's search for healing and wellbeing. The article argues that, especially in the context of high levels of HIV stigma in Ghana, spiritual therapy is one pragmatic option available to people living with HIV as it helps them to find meaning to their predicament or extends their coping mechanisms. [ABSTRACT FROM AUTHOR]