Appropriately designed randomized controlled studies (RCTs) are pivotal for the clinical evaluation of new treatments, but also of new diagnostic tests. Before addressing RCTs, this chapter describes the observational study designs. A case-control study has a retrograde direction of enquiry, it starts with the outcome and looks back at the exposure. Cross-sectional studies are most appropriate for obtaining clinical information before embarking on more elaborate types of study. In an RCT two randomization procedures take place, the first (r1) is the random drawing of a representative sample from the general population, and the second (r2) random allocation of these individuals to either of (most often) two treatment arms. Next, the outcome of treatment is studied and compared between arms. Generation of a proper randomization sequence takes little time and effort but affords big rewards in scientific accuracy and credibility.