Because cancer care is presently developing into a complicated network of interventions delivered at different times and places with different intentions, there is a need to consider whether the current research approaches in clinical cancer care adequately cover the ongoing treatment choices and combinations. Researchers in complementary and alternative medicine (CAM) are proposing whole systems research as an additional research approach for modern systems of care, whether they include complementary and alternative medicine or not. The current status of whole systems research methodology development is mainly theoretical. Necessary components of the methodology include focus on interventions, context, process, outcomes, and philosophy. Further development should be based on observational studies using both qualitative and quantitative approaches, often combined. Only when modern healthseeking systems of treatment behaviors are thoroughly understood should fine-tuning of hypothesis-testing research methods be continued.