Past research suggests that patients' self-management behavior and knowledge about their condition/treatment may impact functioning and well-being. Specific self-management activities used by patients on hemodialysis have included cooperative/participatory and protective/proactive strategies. In this cross-sectional study, measures of self-management and knowledge were administered to 372 patients on hemodialysis-from 17 dialysis facilities. Findings suggest that the patients studied were low self-managers. The most commonly used self-management strategies were the cooperative/participatory activities of self-care during hemodialysis and shared responsibility in care. Multiple linear regression showed self-care during hemodialysis to be positively associated with physical functioning, measured by the SF-12 Physical Component Summary (PCS-12) scale. Age, diabetes, and two protective/proactive strategies (selective symptom management and assertive self-advocacy) were negatively associated with the PCS-12. Selective symptom management was also negatively associated with mental health functioning measured by the SF-12 Mental Component Summary (MCS-12), whereas patient knowledge of kidney disease/treatment was positively associated with the MCS-12. Because past research has shown the SF-36 PCS and the MCS scores to be associated with mortality and hospitalizations, using cooperative/participatory self-management behaviors, minimizing the need for protective/proactive strategies, and increasing patients' knowledge of kidney disease may have long-term benefits.