Background: People with chronic illness are particularly dependent on adequate health literacy (HL), but often report difficulties in accessing, understanding, appraising, and applying health information. To strengthen the HL of people with chronic illness, in-depth knowledge about how they deal with health information is crucial. Methods: To this end, quantitative data from the Second Health Literacy Survey Germany (HLS-GER 2) and qualitative data from seven focus group discussions were used to examine the interest in health information, preferred sources of information as well as experiences and challenges with information management among people with chronic illness. Results: The results show that people with chronic illness have a great interest in health information and use very different sources of health information, preferring personal information from physicians most. The results also point to several challenges in health information management that seem to be influenced by the illness duration as well as by the experiences made with the respective sources. Conclusions: Overall, the study provides important starting points for intervention development for the provision and communication of health-related information, but also to research on health information behavior and HL.