This article examines drug adherence in relation to changing patterns of medical pluralism and neoliberal reforms among psychiatric patients in postreform Ho Chi Minh City, Vietnam. We conducted 39 in-depth interviews and 21 follow-up interviews with individuals prescribed psychiatric medication on an outpatient basis in 2016 to identify patterns of nonadherence, which was operationalized as taking medications according to doctors’ prescriptions at the three-month follow-up interval. Patients adapt or reject their medication prescriptions due to (1) concerns about biomedical drugs and adverse drug reactions, (2) local concepts of psychic distress and selfhood, and (3) the social context of medicine taking. The dominant theoretical models of drug adherence focus on individual-level predictors. However, situating drug adherence in its political-economic context highlights the relationship between medicine and neoliberal modernity that underlies adherence. Examining the intersection of multiple medication regimens and political regimes, we argue that nonadherence is rooted in a complex layering of medical traditions and modernist projects of the self. The reception of new biomedical drugs in Vietnam is shaped by not only folk theories of illness but also a changing cultural politics of the self.