Given the high incidence and prevalence of cancer in older adults and the anticipated growth of this population over the next few decades, oncologists, geriatricians, and primary care providers will be challenged to provide timely and appropriate post-treatment care to a diverse population of older cancer survivors. To the authors' knowledge to date, few post-treatment epidemiologic or clinical trial studies have investigated the mental, social, and physical health issues among older cancer survivors. For this article, the authors reviewed the behavioral oncology, gerontology, geriatric, and psychology literature on cancer survivorship and aging. This report highlights several methodologic challenges that investigators face when conducting epidemiologic and cancer clinical trial research with older cancer survivors after treatment. These challenges must be considered and overcome to develop an informative body of scientific knowledge to address the post-treatment healthcare needs of this growing population. Future research directions, new models of care, and the need for transdisciplinary approaches are discussed.