A new class of medications, protease inhibitors, has dramatically improved the health of many people with Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS). This development has had a major impact on the lives of those affected by HIV/AIDS. This article considers how a group is affected by the larger systems of which it is a part. The article examines changes in the content, process, and salient leadership tasks of an ongoing therapy group for people with HIV and AIDS before and following the initial introduction of new medical treatments. It also considers how the group process continues to be affected by the more recent failure of these medications for many patients. Implications for research, practice, and training are discussed.