Poverty is a global public health problem with profound moral implications about what it means to be [a]part of the human community. In the United States, one in eight persons lives below the federal poverty line, a metric widely believed to underestimate the scope of the problem. While several ethnographies have described communities affected by poverty, far less research has focused on the personal toll of being poor in an urban area while struggling with a serious illness. Dignity is a concept addressed in human rights declarations, discussed in theological and philosophical descriptions of personhood, and described in clinical contexts relating to end of life care, physician assisted suicide, aging and disabilities. The purpose of this primarily interpretive study was to describe the meaning and experiences of dignity to the urban poor with advanced disease using a mixed methods design. First person in-depth accounts through individual or group interviews and field notes were primary data sources; a survey examined Chochinov's inductively derived model of dignity. Participants included 31 adults, with an average age of 52 years, who were living with cancer, HIV disease or both illnesses. Participants had multiple vulnerabilities: almost 75% were from communities of color and approximately two thirds had histories of homelessness, substance abuse, or other co-morbidities. Ten participants died during data collection. Many participants discussed respect rather than dignity, respect given to and received from others, and self-respect. Most narrated difficult personal biographies that included the loss of beloved family members and other traumas. While describing their illness experiences, difficulties with health care systems and health care providers were noted frequently and described in vivid detail. Participants were significantly (p <.001) more likely to report a severe loss of dignity as a result of illness than advanced cancer patients in Canada; many also reported a severe loss of dignity prior to illness. Understanding the everyday lives of the urban poor with advanced disease is essential for providing care that appreciates their humanity and recognizes their struggles to manage illness and treatment demands, as well as for creating environments that are more responsive to their needs.