Co-morbid psychiatric disorders are relatively frequent in patients with epilepsy. The prevalence rates of mood and anxiety disorders, psychotic disorders and attention deficit/hyperactivity disorder have been found to be significantly higher in patients with epilepsy than in the general population. While co-morbid psychiatric disorders have frequently been considered as complications of the seizure disorder, there is an increasing body of literature that points to a complex relationship between psychiatric and seizure disorders. Because of this, it is crucial that clinicians consider the presence of co-morbid psychiatric disorders when planning the treatment of patients with epilepsy. Having a clear understanding of the pharmacodynamic and pharmacokinetic interactions between antiepileptic drugs and psychotropic drugs is of the essence to avert unnecessary adverse events and loss of efficacy of psychotropic drugs. This chapter provides a practical review on the use of psychotropic drugs for the treatment of these psychiatric co-morbidities in patients with epilepsy.