Youth homelessness is a growing Australian and international concern associated with considerable health disadvantage, including serious mental health problems. This paper reports findings of a qualitative study that explored young homeless people's experiences of mental health and well-being through in-depth interviews. Thematic analysis identified medication use and management as a central issue for the young people. Reasons identified for medication non-adherence included unwanted side-effects, issues of access and storage, and lack of support from health and social agencies. These problems were compounded by everyday stresses of homelessness. Medication adherence was facilitated by social support, consistent contact with supportive health services, and regular medication supply, often resulting in improved mental health and well-being. For these young people, prioritizing management of medication helped stabilize one aspect of their lives. Health professionals can play an important role in helping them achieving this goal.