Lithium is an important medication in the treatment of mood disorders. However, clinicians are hesitant to use lithium in older adults for fear of its medical effects, particularly kidney disease. This review describes the current understanding of the epidemiology and mechanisms underlying chronic kidney disease (CKD) in older lithium users, with recommendations for using lithium safely in late life. Prevalence estimates of CKD in older lithium users range from 42-50%, which does not differ greatly from the 37.8% rates seen in community-dwelling non-lithium using, non-psychiatric populations. Clinical and pre-clinical data suggest a variety of synergistic mechanisms contributing to CKD in older lithium users, including aging, cardiovascular factors, oxidative stress, inflammation, nephrogenic diabetes insipidus, acute kidney injury, and medication interactions. With regards to CKD, lithium can be used safely in many older adults with mood disorders. Compared to patients with pre-existing CKD, those with an estimated glomerular filtration rate >60 mL/min/1.73 m(2) are probably not as susceptible to lithium-associated renal decline. Using lithium concentrations <0.8 mmol/L; monitoring lithium concentrations and renal function every 3-6 months; being vigilant about concurrent medication use (e.g., diuretics, anti-inflammatories); as well as preventing/treating acute kidney injury, nephrogenic diabetes insipidus, diabetes mellitus, hypertension, smoking, and coronary artery disease can all help prevent CKD and further renal decline in older lithium users.