The precipitous decline of memory and independence associated with cognitive decline, dementia, and Alzheimer's disease is emotionally and financially devastating to patients, their families, and caretakers. Studies from animal models and cell cultures have shown that omega-3 fatty acids (n-3 FAs) are neuroprotective during development and aging. Numerous epidemiologic, postmortem, and clinical trials have been published on fish or n-3 FAs and Alzheimer's disease, dementia, or cognitive decline. Yet results across the literature in humans are inconsistent and thus difficult to interpret. This review provides background and context needed for interpretation of the findings, summaries of the literature grouped by longitudinal studies of fish, dietary n-3 FAs, blood levels of fatty acids, postmortem studies, and clinical trials, and subsequent interpretation of findings. Possible reasons for discrepancies in the literature are presented throughout, and conclusions suggest directions for future research.