A diverse panel convened in June 2011 to explore a dilemma in human research: some traits may make individuals or communities particularly vulnerable to a variety of harms in research; however, well-intended efforts to protect these vulnerable individuals and communities from harm may actually generate a series of new harms. We have presented a consensus statement forged by the panel through discussion during a 2-day meeting and the article-writing process. We have identified practical problems that sometimes arise in connection with providing additional safeguards for groups labeled as vulnerable and offered recommendations on how we might better balance concerns for protection with concerns for justice and participant autonomy.