In medically ill patients, anxiety symptoms and mood alteration are common. Anxiety or mood alteration may be due to a reaction to the stress of illness, a preexisting psychiatric disorder, a manifestation of the medical condition, or an adverse effect of medication. Psychiatrists are frequently called upon to differentiate among these causes and to recommend treatment. This article reviews anxiety, depression, and mania, which are frequently associated with physical disease, and provides an approach to differential diagnosis and treatment.