In vitro dissolution study should ideally be designed to predict in vivo performance precisely, providing key information on the bioavailability and establishing IVIVC. Development of discriminatory in vivo predictive dissolution model and the establishment of IVIVC is difficult to achieve with BCS Class 2 drugs as they exhibit variable absorption along the GI tract owing to pH-dependent solubility, especially for Classes IIa and IIb. In this context, the biphasic dissolution model is a powerful technique for investigating the interplay between dissolution, precipitation and partitioning of various poorly soluble molecules. The dissolution test medium comprising of immiscible aqueous and organic phases enables maintenance of sink conditions and easy quantification of poorly soluble drug partitioning into the organic phase. In the review, novel efforts have been taken to provide comprehensive information on challenges associated with the establishment of IVIVC for BCS Class II drugs, various approaches being adopted for developing discriminatory in vivo predictive dissolution model, significant outcomes of studies on biphasic dissolution model to predict the in vivodissolution behaviour of BCS Class II drugs and the problems with the use of biphasic dissolution model including the status of FDA on the same.