Exercise improves quality of life (QOL) in people with cancer. Most oncology healthcare providers recognize the statement to be true because the research literature provides strong support for the physical and psychological benefits of exercise. Because the terms exercise, QOL, and people with cancer have different meanings, the contextual connections in which they are used are important to understanding the relationship between exercise and QOL in people with cancer. This article explores the links between exercise and QOL in people with cancer and examines issues that impact the development, implementation, and evaluation of exercise programs for people with cancer. Issues related to exercise goal development, exercise prescription, exercise testing, exercise adherence, and methods to evaluate the efficacy of exercise in relation to QOL are discussed.