We risk ignoring cheaper and safer medical treatments because they cannot be patented, lack profit potential, require too much patient-contact time, or do not have scientific results. Novel medical treatments may be difficult to evaluate for a variety of reasons such as patient selection bias, the effect of the package of care, or the lack of identifying the active elements of treatment. Whole Systems Research (WSR) is an approach designed to assess the performance of complete packages of clinical management. While the WSR method is compelling, there is no standard procedure for WSR, and its implementation may be intimidating. The truth is that WSR methodological tools are neither new nor complicated. There are two sequential steps, or boxes, that guide WSR methodology: establishing system predictability, followed by an audit of system element effectiveness. We describe the implementation of WSR with a particular attention to threats to validity