This article reports on the findings of a study conducted with a sample of 136 Mexican-heritage mothers residing in a large southwestern metropolitan area. From a risk-and-resiliency perspective, hopelessness was approached as a culturally specific response to family stress and other challenges encountered by Mexican immigrants. Although Mexican-heritage women and other Latinas have higher prevalence rates of psychiatric disorders than their male counterparts, they experience disparity in accessing mental health services. Multiple regression analysis was used to explore the relationships among hopelessness, depression, social support, and other variables. Culturally rooted resiliency and a sense of optimism connected to immigration appear to shelter Mexican-heritage mothers from hopelessness and depression. A very large households and nonworking status were found to elevate the risk of hopelessness. Because poverty and acculturation levels were not related to hopelessness or depression, further culturally specific research distinguishing hopelessness from depression is recommended. Given that hopelessness sometimes presents itself independently from depression, implications for practice include the need to refine mental health assessment tools to capitalize on the resiliency among immigrant mothers and avoid misdiagnosis.