This chapter reviews the existing literature on the relationship between sleep and mood disorders, in particular, treatment-resistant disorders. It also reviews the subjective and objective changes in sleep that occur in depressive and manic episodes, and describes how these sleep findings may be predictive of treatment-resistant states. Normal sleep consists of alternating rapid eye movement (REM) and non-REM epochs. Deliberate sleep deprivation produces an antidepressant effect in major depressive episodes (MDE) patients. While acute sleep deprivation can be beneficial for symptoms of depression, like any effective therapy, there are side effects. For some depressed individuals, sleep deprivation simply induces fatigue. The application of sleep deprivation to treat treatment-resistant depressions and sleep induction to treat treatment-resistant manic states holds promise. The relative contribution of primary sleep disorders to treatment-resistant mood states is virtually unknown and warrants investigation.