Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic and treatment process that identifies the medical, psychosocial, and functional capabilities of older adults in order to develop a coordinated management plan. No standard criteria are available to readily identify subjects who are likely to benefit from CGA. Recent evidences suggested that the healthcare setting may modify the effectiveness of CGA programmes. Home CGA programmes and CGA performed in the hospital, especially in dedicated units, have been shown to be consistently beneficial for several health outcomes. In contrast, the data are conflicting for post-hospital discharge CGA programmes, outpatient CGA consultation, and CGA-based inpatient geriatric consultation services. The effectiveness of CGA programmes may be influenced also by particular settings or specific clinical conditions, with tailored CGA programmes for older frail patients evaluated for preoperative CGA, admitted or discharged from emergency departments and orthogeriatric units, or with cancer, organ failure, and cognitive impairment.