It was conducted a systematic review of economic evaluations that assessed the cost-effectiveness of interventions to enhance the medication adherence in psychiatric patients. Several bibliographic databases were searched: MEDLINE, MEDLINE in process, PSYCINFO, EMBASE, Cochrane Controlled Trials Register, CINAHL, CRD, EconLit, Science Citation Index and Social Science Citation Index. Full economic evaluations which assessed interventions to enhance the adherence to drug therapy in adult patients with a mental illness were included. Data were extracted and the methodological quality of selected studies was assessed. The information was synthesized through narrative procedures. Four clinical trials and two ongoing studies fulfilled the selection criteria. Two studies did not find significant differences in adherence between the interventions (a compliance-enhancing program, a therapeutic drug monitoring and a pharmacy-based intervention) and the control groups; one study found that a compliance program was more effective than a non-specific counselling intervention over 18 months in psychotic patients; another study found better results in terms of adherence among high-severity depressed patients receiving a stepped collaborative care during 12 months in comparison to a control group; in moderate-severity patients the differences disappeared after the first 6 months. None of the four studies found significant differences in costs between groups because of the low statistical power. In summary, adherence enhancing programs could be cost-effective in psychiatric patients although this statement is based on few studies with limited methodological quality. It is necessary more and better research on the cost-effectiveness of interventions in the field of mental health.