This chapter provides an overview of the principles of pharmacotherapy for disorders of mood and affect. Major depressive disorder is the most common primary mood disorder. The clinical presentation of major depressive episodes may be obscured by neurological conditions. Changes in weight, sleep, activity, thinking, and fatigue are common symptoms of many neurological conditions. Depression is common among persons with neurological disorders such as cerebrovascular disease, traumatic brain injury (TBI), epilepsy, multiple sclerosis (MS), Alzheimer's disease (AD), and Parkinson's disease (PD), among others, and depression in these patients worsens the outcome of the neurological illness. Pathological laughing and crying (PLC) describes a syndrome of affect dysregulation characterized by brief, intense, frequent episodes of uncontrollable laughing and/or crying that are provoked by non-sentimental or trivially sentimental stimuli. Mood stabilizers are used to treat bipolar disorder. Antipsychotic drugs are usually necessary adjuncts to antidepressants in the treatment of psychotic depression.