A randomized trial of in-home psychotherapy for depressive symptoms that targeted low-income mothers of infants and toddlers used innovative design features to reduce stigma and enhance acceptability. Despite these features, advanced practice psychiatric mental health nurses used specialized, relationship-based strategies to engage and retain these high-risk mothers in the intervention. Data revealed that the nurses needed to diligently maintain contact, provide encouragement, use empathy for rapid assessment and response, and control the intensity of the relationship-based contacts in order to retain mothers.