The use of hyponeophagia, in which exposure to a novel environment suppresses feeding behavior, has been used to assess anxiety-related behavior in animals for over seven decades. More recent work has shown that variations of hyponeophagia, such as the novelty-suppressed feeding test, have become effective paradigms for testing treatment with drugs such as anxiolytics and antidepressants. Most interestingly, unlike many other behavioral paradigms, novelty-suppressed feeding is sensitive to chronic, but not acute, antidepressant treatment, which mirrors the effects of antidepressant treatment in human patients. Here we provide a brief historical overview of novelty-suppressed feeding and provide a protocol for running the test with mice.