Adjustment Disorder (AD) is one of the most common psychiatric diagnoses employed. In fact, it is the most frequent diagnosis utilized for psychiatric disorders in the military and in children, and is often utilized in the consultation-liaison medical setting. However, it is acknowledged that the diagnosis is not reliable, it cannot be validated, and it has an important degree of subjective consideration in its use. Commonly used screening tools like the Hamilton and Beck Depression Scales do not give an assessment of AD. Furthermore, its use is accompanied with descriptors of depression, anxiety, mixed affects, etc., so that it crosses over several areas of psychiatric dysfunction. It does allow the placement of a patient within a psychiatric diagnosis when they do not reach criteria for a major psychiatric nomenclature. To date, biological studies have not been reported. It is not known if AD with depression is closer to the biological characteristics of depression, or AD with anxiety would have similar characteristics to that seen with major anxiety. It is also not known if AD has a biological signature that would make them an entity with common features, or if they may be more closely allied biologically with the descriptor that accompanies them. Nevertheless, AD is an important category in any psychiatric lexicon and warrants further study and biological understanding.