Bioavailability and bioequivalence studies play a vital role in the development of generic medicines. These studies help us in understanding the drug efficacy and safety and to compare against the reference listed drug (RLD). In the recent years, many debates have emerged about usage of average bioequivalence and whether it’s a right tool for the assessment of narrow therapeutic index drugs and highly variable drugs. In this scenario, alternative approaches like population bioequivalence and individual bioequivalence have emerged. This paper aims to discuss all the important questions concerning whether these approaches, average bioequivalence, population bioequivalence and individual bioequivalence address the drug interchangeability and what is the level of accuracy for the assessment of different categories of drugs such as large therapeutic index drugs, narrow therapeutic index drugs and highly variable drugs. © 2015, Pharmainfo Publications. All rights reserved.