This paper explores how drug treatment clients exercise agency while finding their ability to act curtailed by the strictures of treatment itself. Drawing on interviews with drug treatment clients collected in an Australian study of drug treatment and mental health, the experience of methadone maintenance treatment (MMT) and that of commonly prescribed medications for depression (antidepressants) are examined. The ways that clients engage with MMT and antidepressants are detailed, illustrating how both types of treatment can make clients feel dependent, but can also motivate clients to modify their treatment regimens. These modifications are ‘tactical’ responses generated within the constraints of treatment regulations but can also be against clinical recommendations e.g. stopping treatment. Rather than seeing this as ‘non-compliance’, it is suggested that the negotiation of treatment is an inevitable response of clients who are trying to adapt to imperfect treatment conditions, and who may have understandable anxieties about taking medication. The ways in which treatment providers might better acknowledge the capacities of MMT clients to engage with or modify treatment are discussed, as is the need to acknowledge drug treatment clients’ anxieties about dependency and pharmaceutical drugs.