The rate of cognitive decline in the elderly is highly variable. One potential factor contributing to accelerated cognitive decline is chronic systemic inflammation, because it has been linked to cognitive impairment and increased dementia risk. Certain lifestyle factors, such as excess body weight and sedentary behavior, can exacerbate a proinflammatory state in older adults, resulting in chronic low-grade inflammation. Supplementing the diet with curcumin, an anti-inflammatory polyphenolic compound from the curry spice turmeric, is a potential approach to prevent accelerated cognitive decline by counteracting chronic inflammatory processes. Although the anti-inflammatory effects of curcumin are well established, the potential cognitive benefits of curcumin were discovered more recently. Several animal and epidemiologic studies on the effect of curcumin supplementation on cognition showed promising results; however, randomized controlled trials in humans are limited. In this review, we identified 5 randomized controlled trials, of which only 2 observed a beneficial effect of curcumin supplementation on cognition by improving working memory. By critically examining the methodologies of those studies, we identified some limitations, one of which is that none of the studies explored the possibility that anti-inflammatory mechanisms were mediating cognitive benefits (i.e., no study tested participants with low-grade inflammation or measured inflammatory biomarkers). Other factors influencing the likelihood of conclusive outcomes include choice of study population (cognitively unimpaired compared with impaired), study duration, curcumin dose and its bioavailability, and neurocognitive test battery. On the basis of these findings, we offer recommendations for future studies to examine the potential cognitive benefits of curcumin in humans, which include evaluating its effects on cerebral endothelial vasodilator function and boosting its cognitive effects by combining it with long-chain omega-3 (n-3) fatty acids.