This study examined and assessed the relationship between degree of stigma, level of insight into illness, medication compliance, and patient demographics among seriously and persistently mentally ill (SPMI) adults. The unit of analysis was the individual diagnosed with a serious and persistent mental illness. This was a crosssectional survey design. The sample was recruited from three sites (with nine settings), which included continuing day treatment programs, outpatient psychiatric clinics, supportive residential settings, and consumer empowerment groups for the psychiatric patient. Data was gathered by administering pre-existing, validated instruments which measured attitudes and perceptions about stigma, insight into illness and medication compliance. Study findings are directly relevant to the social work profession because it helps us to understand how stigma, level of insight into illness, medical compliance, affect people with serious and persistent mental illness as they inter-relate and cope with the devastating impact of their illnesses. The findings present practice, administrative, educational and policy implications and can contribute to the development and maintenance of support for SPMI. Mental health service providers, public policymakers, and practitioners must recognize the needs and concerns of these individuals as a basis for planning and delivering effective mental health services.