Neurotrophins such as brain-derived neurotrophic factor (BDNF) play an important role in the proliferation and survival of cholinergic, dopaminergic, and serotonergic neurons. With high BDNF gene expression in the hippocampus and prefrontal cortex, BDNF is a regulatory factor for building and maintaining cognitive reserves. The recently identified BDNF C270T polymorphism is understudied, especially in non-clinical samples. In this study, 106 adults completed a battery of executive function measures and were genotyped using real-time polymerase chain reaction. Results indicated that the C/T group (n = 42) outperformed the C/C (n = 62) group on measures of cognitive flexibility. No genotype effects emerged for domains of abstract reasoning, planning/task initiation, response inhibition, self-monitoring, fluency, or working memory. Although the mechanism of C270T gene expression as it relates to BDNF availability is still unknown, we speculate that the C/T polymorphism modulates phasic dopamine activity in the prefrontal cortex to achieve enhanced cognitive flexibility.