Evidence-based medicine (EBM) stresses the examination of evidence from clinical research and describes it as a shift in medical paradigms, in contrast to intuition, unsystematic clinical experience, and pathophysiologic rationale. While the importance of randomized trials has been created by the concept of the hierarchy of evidence in guiding therapy, much of the medical research is observational. There is competition, contrast, and a feeling of inferiority and uselessness for observational studies, created by a lack of understanding of medical research. However, observational studies and randomized clinical trials (RCTs) can be viewed as the steps of observation and experimentation that form the basis of the scientific methodology. Further, rational healthcare practices require knowledge about the etiology and pathogenesis, diagnosis, prognosis, and treatment of disorders. The reporting of observational research is often not detailed and clear enough with insufficient quality and poor reporting, which hampers the assessment of strengths and weaknesses of the study and the generalizability of the mixed results. Thus, design, implementation, and reporting of observational studies is crucial. The biased interpretation of results from observational studies, either in favor of or opposed to a treatment, and lack of proper understanding of observational studies, leads to a poor appraisal of the quality. Similar to the Consolidated Standards of Reporting Trials (CONSORT) statement for the reporting of randomized trials, the Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) statement was developed with recommendations to improve the quality of reporting observational studies. The STROBE statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Multiple types of observational studies are conducted; however, 3 types have been highlighted in the STROBE document and also in the present review, which include cohort studies, case-controlled studies, and cross-sectional studies. This comprehensive review provides an introduction and rationale, types, design, and reporting of observational studies; outcomes assessment and data presentation and analysis; statistical analysis, results, and a discussion of observational studies.