Purpose: Patients with multiple chronic conditions (multimorbidity) often require ongoing treatment and complex self-care. This workload and its impact on patient functioning and well-being are, together, known as treatment burden. This study reports on factors that patients with multimorbidity draw on to lessen perceptions of treatment burden. Patients and methods: Interviews (n=50) and focus groups (n=4 groups, five to eight participants per group) were conducted with patients receiving care in a large academic medical center or an urban safety-net hospital. Interview data were analyzed using qualitative framework analysis methods, and themes and subthemes were used to identify factors that mitigate burden. Focus groups were held to confirm these findings and clarify any new issues. This study was part of a larger program to develop a patient-reported measure of treatment burden. Results: Five major themes emerged from the interview data. These included: 1) problem-focused strategies, like routinizing self-care, enlisting support of others, planning for the future, and using technology; 2) emotion-focused coping strategies, like maintaining a positive attitude, focusing on other life priorities, and spirituality/faith; 3) questioning the notion of treatment burden as a function of adapting to self-care and comparing oneself to others; 4) social support (informational, tangible, and emotional assistance); and 5) positive aspects of health care, like coordination of care and beneficial relationships with providers. Additional subthemes arising from focus groups included preserving autonomy/independence and being proactive with providers. Conclusion: Patients attempt to lessen the experience of treatment burden using a variety of personal, social, and health care resources. Assessing these factors in tandem with patient perceptions of treatment burden can provide a more complete picture of how patients fit complex self-care into their daily lives. © 2014 Ridgeway et al. This work is published by Dove Medical Press Limited.