Therapeutic monitoring of drugs is a well established clinical tool. However, the state of the art is somewhat less advanced for drugs used in psychiatry than it is for other classes of drugs, for several reasons. Most psychotherapeutic drugs have large volumes of distribution and achieve relatively low plasma concentrations following therapeutic doses. Many have one or more active metabolites. While psychotherapeutic drugs act through biochemical mechanisms, they are used to treat clinical syndromes which may be heterogeneous in their biochemical pathogenesis. As a consequence, the analytical methodologies are often complex and not always reliable; well-controlled clinical studies are difficult to perform; the therapeutic ranges have been difficult to establish. Despite these limitations, prudent and selective monitoring of serum drug concentrations, particularly of the tricyclic antidepressants, can be helpful in clinical management.