The spectrum of evidence imparted by the different clinical research designs ranges from ecological studies through observational epidemiological studies to randomized control trials (RCTs). This chapter addresses the definition of clinical research, the major aspects of clinical trials eg ethics, randomization, masking, recruitment and retention of subjects enrolled in a clinical trial, patients/subjects lost to follow-up during the trial etc. Although this chapter focuses on the weaknesses of clinical trials, it is emphasized that the randomized, placebocontrolled, double blind clinical trial is the design that yields the greatest level of scientific evidence. A researcher is in a gondola of a balloon that loses lift and lands in the middle of afield near a road. Of course, it looks like the balloon landed in the middle of nowhere. As the researcher ponders appropriate courses of action, another person wanders by. The researcher asks, 'Where am I?' The other person responds, 'You are in the gondola of a balloon in the middle of a field.' The researcher comments, 'You must design clinical trials.' 'Well, that' amazing, how did you know?' 'Your answer was correct and precise and totally useless.' © Springer Science + Business Media B.V. 2008.