In the spring of 2012, a nurse in Washington State detected a cluster of babies born with anencephaly—a fatal condition in which infants are born without parts of the brain or skull. The resulting investigation initially confirmed a rate of anencephaly between January 2010 and January 2013 of 8.4 per 10,000 live births—more than four times the national average. As of November 2015, cases of anencephaly in Washington State have continued to increase, with the current rate estimated at 9.5 per 10,000 live births. While no distinct cause has yet been determined, neural tube defects—including anencephaly—are known to have multiple causes, including folic acid deficit, genetic variants in the folate pathway, and exposure to a variety of environmental and occupational toxins. This article describes many of these risk factors and explores the findings of Washington's ongoing investigation.