It was within my first week of arriving as a medical informatics research fellow that Dr. Clem McDonald began to instill the axiom that life is hard. Dr. McDonald is the director of the Regenstrief Institute, Inc, Director of the Informatics Fellowship Program, and a pioneer in the field of medical informatics -- the field that seeks to advance healthcare through information technology. With over 30 years of experience in designing, implementing, and researching computer systems in clinical care, he understands the inherent complexity of trying to introduce a relatively rigid technology into the dynamic fabric that is our healthcare delivery system. When computer systems are integrated into the care environment, complex and rarely predictable behaviors emerge out of the social-technical interactions.[1] While they may not often be thought of as clinical interventions, electronic systems must be studied with rigorous trials to define whether or not they can measurably improve care. Clinical informaticians, the investigators who design and evaluate health information systems, are presented with a unique set of challenges in conducting controlled trials.