The concepts of health and self have become intimately entangled in contemporary western society. Health is figured as a marker of identity, as a vehicle of self-production and selfactualisation, while the individual is also made increasingly responsible for his or her health. In this paper, we explore how “self” is constituted in discourses that shape the ways in which people understand and do health and medicine, particularly discourses of neoliberalism and of the immune system. Of interest here is how the productive and unpredictable intra-action of medicine and bodies may come to trouble these discursive selves. Drawing on qualitative interviews, we situate our discussion in the context of efavirenz, an antiretroviral drug prescribed and consumed for the treatment of HIV infection. This drug, commonly described as “potent”, can have a number of troubling effects on a person’s everyday sense of self, including insomnia, confusion, cognitive disorders, depression, depersonalisation, psychosis, and suicidal ideation. While efavirenz may be clinically effective in its capacity to suppress the virus, these effects are at odds with the implicit aim of HIV medicine to restore and secure the self by way of immunological integrity and strength. These effects also bring into focus the predicament of choice under the contemporary political conditions of neoliberalism with its emphasis on health as an enterprise of the autonomous, rational self. In exploring first person accounts of efavirenz, the paper unpacks a number of the binary concepts on which contemporary discourses of health and medicine rely, such as immunity and vulnerability, potency and fragility, rationality and madness, self and non-self, and asks whether the individual under neoliberalism is being asked the impossible.