With the biological relevance of the whole cells, low cost compared with animal experiments, a wide variety of cell-based screening platforms (cell-based assay, cell-based microfluidics, cell-based biosensor, cell-based chromatography) have been developed to address the challenges of drug discovery. In this review, we conclude the current advances in cell-based screening and summary the pros and cons of the platforms for different applications. Challenges and improvement strategies associated with cell-based methods are also discussed.