OBJECTIVE The aim of this study is to provide information about lithium effectiveness and safety in the treatment of old patients with mood disorders. METHODS The study is naturalistic in nature and design and considers all patients aged ≥75 years attending our center in the past 10 years. We obtained patients' socio-demographic and clinical characteristics, the worst Global Assessment of Functioning score assigned in the course of treatment, the Clinical Global Impression (CGI) score at the beginning of treatment, the CGI-Improvement (CGI-I) highest score achieved in the follow-up, and drop-out rates. We compared patients treated with lithium, in some cases associated with other psychotropic medications, and patients treated with psychotropic medications other than lithium. Furthermore, we analyzed lithium side effects and causes of lithium withdrawal. RESULTS In the considered period, 25 lithium-treated patients achieved higher CGI-I scores after treatment in comparison with 138 patients not receiving lithium. Drop-out rates were similar in the two groups. Mean dose of lithium was 390 ± 178.5 mg/day. Among lithium treated patients, neither hypothyroidism nor renal failure were significant problems. Thyroxine treatment was prescribed to 8 (32%) lithium-treated patients. Lithium was withdrawn in 6 (24%) patients, respectively for ineffectiveness, heart disease (unrelated to lithium), erratic and unpredictable metabolism of lithium, poor compliance (two cases), and mitigation of the disease. CONCLUSIONS Lithium remains irreplaceable and maintains a high effectiveness in the treatment of elderly patients. Low doses and frequent monitoring are recommended.