Relapse of severe depression after successful treatment with electroconvulsive therapy (ECT) continues to be a major problem. We review the literature on relapse after ECT and factors that predict relapse. Early studies showed that the relapse rate was ∼50% without follow-up treatment and that the majority of these relapses occurred in the first 6 months. More recent studies have found even higher rates in delusional depression and possibly in “double depression.” Studies of biological markers as predictors of relapse were examined. Six of nine studies of the dexamethasone suppression test and one study of cortisol hypersecretion show that post-ECT nonsuppressors are at higher risk; although insensitive for diagnostic purposes, this test may be useful, when persistently abnormal, as a predictor of relapse. Studies of the thyrotropin-releasing hormone stimulation test and shortened rapid eye movement sleep latency are inconclusive. Medication resistance pre-ECT has been shown to predict relapse in two studies and highlights the need for more aggressive and effective treatment in this group. Further research into the prediction and prevention of depressive relapse after ECT is needed, and the field anxiously awaits current trials comparing ECT with combination lithium and nortriptyline.