Tricyclic Antidepressants (TCAs) and Monoamine Oxidase Inhibitors (MAOIs) remain useful pharmacotherapies for pediatric psychiatric disorders despite the fact that they are no longer used as first line medications. In pediatric populations, evidence supports the use of TCAs as second or third line treatment for several disorders including OCD, ADHD, and some pain disorders. While less evidence supports the use of MAOIs in youth, the selegiline transdermal patch is currently under investigation and may provide a viable alternative for the treatment of pediatric psychiatric illness. This chapter describes the chemical properties, indications, treatment guidelines, and side effect profiles of both TCAs and MAOIs in the treatment of children and adolescents. © 2012 John Wiley & Sons, Ltd.