Evidence-based medicine (EBM) is a science in itself which paves way for effective utilization of healthcare literature in medical practice. EBM is not only about overcoming subjective judgment, tradition, and authority in medical practice, but to impart other values such as patient preferences and choices along with best-available evidence. Hence, EBM can be considered as a “patient-centred” approach to clinical decision-making. Currently, EBM lies at the core of clinical practice. EBM tends to integrate “clinical epidemiology” and “biomedical research” – by imbibing and applying their concepts, “statistical analysis” and “scientific methodology”, respectively. The real purpose of EBM was to harness the incremental increase in biomedical data and ever-expanding medical knowledge – with far few “real” breakthroughs – and make the “busy” clinicians to adopt and implement the “best” available evidence efficiently in day-to-day clinical practice. Initially, EBM was essentially focused on three major domains, namely, critical appraisal of available literature, development of systematic reviews, and clinical practice guidelines. All along these years, it is observed that EBM had contributed heavily to clinical medicine in the following ways, as quoted by Guyatt (the scientist who had introduced the term “Evidence-Based Medicine”, 35 years ago) himself, shifting the practice of medicine on the base of scientific judgement, delineating the complex evidence hierarchies, prioritizing the patient values and preferences in clinical decision-making, and in the development of more robust methodologies for producing trustworthy guidelines and recommendations. In this chapter, the definitions, evolution, current status, progress, and future of EBM are deliberated extensively.