Medical contraindications and complications pose challenges for electroconvulsive therapy (ECT). Most published reports are scattered across various physiological systems and individual disease conditions. This review aimed to evaluate the literature on physiological and medical complexities during ECT and discuss risk mitigation strategies in a comprehensive review. We searched PubMed and Embase for contraindications and precautions during ECT with relevant MeSH terms and appraised previous reviews on the same topic. The results suggest that mortality directly attributed to ECT is extremely rare. Instances of fatalities, including fetal deaths, have been reported after ECT in the presence of recent myocardial infarction, deep vein thrombosis, intracranial aneurysm and tumors, pheochromocytoma, sepsis, and pregnancy. However, there are no definite conclusions or consensus on attributions of the outcomes to ECT in all cases because of the time lag between the treatment and deaths and confounding factors. The risks can be mitigated with safety protocols, adequate stakeholder communication, collaboration with anesthetists and specialists, consultation-liaison services, and ECT education. Overall, ECT remains a relatively safe treatment even in the presence of medical and physiological complexities. In rare instances, certain medical conditions may indicate a high risk for ECT, where practitioners avoid the treatment or administer it with precautions if the risk-benefit ratio favors its use.