Maternal depression, although prevalent in low-income women, is not an inevitable consequence of poverty. Nevertheless, depression is a double burden for impoverished women: compromising infant development and diminishing mothers' ability to benefit from or effectively use home visiting services. Without universal screening, depression is often missed. The trust and rapport that home visitors establish with mothers uniquely positions them to screen for depression. Yet, implementing universal depression screening is a complex undertaking. This article provides a pragmatic overview of the key elements of a universal screening program followed by a case study exemplar of universal depression screening in the Des Moines Healthy Start Project.