An optimal treatment of psychiatric patients requires a good collaboration between patients, treating physicians, clinical pharmacologists and the laboratory, if therapeutic drug monitoring (TDM) is part of the treatment strategy. Unfortunately, there is a risk for non-compliance at all levels. Prevalence of non-compliance in patients with schizophrenia is estimated to reach 40-70% while, e.g., doses lapses of at least 2 days were observed in 30% of depressive patients treated with SSRI during 90 days. Poor compliance is an important risk factor for non-response, relapse and adverse effects. TDM of psychotropic drugs such as antidepressants, antipsychotics and mood regulators is widely introduced in psychiatry and non-compliance constitutes one of its main indications as summarized recently in a Consensus paper about TDM in psychiatry (Baumann et al., Pharmacopsychiatry 37 (2004) 243). Other indications for TDM in psychiatry are poor response or non-response, somatic comorbidities which need comedication, longterm treatments, relapses: all these situations have also to be considered as risk factors for poor compliance. Indicators for non-compliance are drug plasma concentrations well below those considered as normal for a particular dose, or fluctuating levels which suggest irregular drug intake. However, several studies have also shown that prescribing physicians may present poor compliance in the treatment of psychiatric patients, in that the use of TDM is not carried out adequately. A model will be discussed, which presents the different prerequisites for an optimal treatment taking compliance into account (M‥uller et al., Pharmacopsychiatry 36 (2003) 98).