There is a dire need to establish transparent medication safety guidelines and to assure the public of the industry’s commitment to this task. Clinical investigators and their staffs who conduct clinical trials often do not understand some of the regulatory methodology used to assess medication safety, particularly with regard to the assignment of causality to drug-related Serious Adverse Events. Yet, this is critical to establish the safety of medication. The medical monitor in a clinical trial can help educate and guide investigators in a clinical study with regard to accepted causation assignment. Since there is a paucity in the literature regarding medical monitoring of clinical trials, this article will help to fill this gap, and to provide a guide to establishing proper causality of an adverse event. This open access article can be found at “Medical Monitoring of Clinical Research Studies”.