Each year, hundreds of thousands of women in the United States confront significant medical illness while pregnant: Hypertension, diabetes, serious psychiatric illnesses, autoimmune diseases such as arthritis and lupus, and even cancers complicate pregnancies. Yet we face a critical dearth of information about how to treat them. Little is known about how drugs work in their bodies, whether those drugs are safe for the fetus, and the extent to which treatment or nontreatment affects maternal and child health (Chambers, Polifka, and Friedman 2008; Fisk and Atun 2008). Recently, a groundswell of attention has begun to highlight the urgent need to garner adequate evidence for the treatment of pregnant women who face illness (Lyerly, Little, and Faden 2008, 2009; Baylis 2010; Macklin 2010). The National Institutes of Health Office of Research on Women’s Health convened a research forum on enrolling pregnant women in research on October 18, 2010 that emphasized both the imperative for and early work on such research; the Obstetric-Fetal Pharmacology Research Unit (OPRU) Networkand the Microbicide Trials Network have begun to pioneer innovative models for research involving pregnant women. The Second Wave Initiative—so named because it calls for a second wave of efforts to follow the legislative and other work of the 1990s promoting fair representation of nonpregnant women in research—has worked to bring together scientists, regulators, and bioethicists to focus attention on the issue. All have issued a clarion call: As a matter of health for pregnant women and children, and of justice, we need to finally address what the broader and otherwise successful Women’s Health Initiative left behind—the profound lacuna that is evidence-based treatment during pregnancy.