Recognizing multiple neuropathological entities in people with dementia improves understanding of diagnosis, prognosis, and expected outcomes from therapies. Care for the individual with dementia includes the evaluation and management of diseases associated with the aged brain, most commonly neurodegeneration and vascular brain injury (VBI). Terminology has evolved to keep pace with diagnostic, prognostic, and therapeutic advances, and autopsy studies have shown that multiple comorbid neuropathological entities are the rule, not the exception, especially in older individuals. With the advent of disease-modifying therapies, delivering dementia care requires an encompassing framework that allows clinicians to consider all of an individual's underlying diseases and their contributions to symptom burden. A diagnostic approach, common co-occurring pathologies, and implications for current and future clinical care are reviewed.