OBJECTIVE: Cure rates for cancer are increasing, especially for breast, prostate, and colorectal cancer. Despite positive trends in survivorship, a cancer diagnosis can trigger accelerated functional decline that can threaten independence, reduce quality-of-life and increase healthcare costs, especially among the elderly who comprise the majority of survivors. Lifestyle interventions may hold promise in reorienting functional decline in older cancer survivors, but few studies have been conducted. METHODS: We describe the design and methods of a randomized controlled trial, RENEW (Reach out to ENhancE Wellness), that tests whether a home-based multi-behavior intervention focused on exercise, and including a low saturated fat, plant-based diet, would improve physical functioning among 641 older, long-term (>or=5 years post-diagnosis) survivors of breast, prostate, or colorectal cancer. Challenges to recruitment are examined. RESULTS: Twenty thousand and fifteen cases were approached, and screened using a two-step screening process to assure eligibility. This population of long-term, elderly cancer survivors had lower rates of response (approximately 11%) and higher rates of ineligibility (approximately 70%) than our previous intervention studies conducted on adults with newly diagnosed cancer. Significantly higher response rates were noted among survivors who were White, younger, and more proximal to diagnosis and breast cancer survivors (p-values<0.001). CONCLUSION: Older cancer survivors represent a vulnerable population for whom lifestyle interventions may hold promise. RENEW may provide guidance in allocating limited resources in order to maximize recruitment efforts aimed at this needy, but hard-to-reach population.