During the past several decades, neuropsychiatric agents have been one of the fastest growing classes of medicinal agents. This expansion is in part due to the increased recognition of the prevalence and burden of illness associated with disparate neuropsychiatric disorders, increased public awareness and possibly reduced stigma associated with mental illness, as well as extensive marketing of neuropsychiatric agents to healthcare providers. Most of the agents reviewed herein represent modifications and/or refinements of pre-existing agents and/or theoretical approaches (e.g., monoamine hypothesis). There remains a relative paucity of agents with genuinely novel mechanisms targeting effector systems implicated in contemporary models of disease pathophysiology in mood and psychotic disorders (e.g., glutamate, insulin, brain derived neurotrophic factor and other growth factors, immunoinflammatory systems and oxidative stress).