The article discusses the importance of three-dimensional (3D) cell culture in drug discovery, particularly for anti-cancer drugs. It highlights the limitations of two-dimensional (2D) cell cultures, which often fail to mimic the in vivo environment and can lead to inaccurate predictions of drug efficacy and safety. The authors review various 3D culture methods, including forced-floating, hanging drop, spinner flask bioreactors, rotating cell culture bioreactors, and the use of matrices and scaffolds. These methods aim to create more physiologically relevant models by mimicking the natural cellular architecture and extracellular matrix (ECM). The article also emphasizes the biological differences between 2D and 3D cultures, such as altered cellular phenotype and sensitivity to drugs. Examples of studies demonstrating the advantages of 3D cultures in drug screening are provided, highlighting their potential to improve the efficiency and success rate of drug development. The authors conclude that incorporating 3D cell spheroids into the drug discovery process can bridge the gap between in vitro and in vivo studies, leading to more effective and less toxic drugs.The article discusses the importance of three-dimensional (3D) cell culture in drug discovery, particularly for anti-cancer drugs. It highlights the limitations of two-dimensional (2D) cell cultures, which often fail to mimic the in vivo environment and can lead to inaccurate predictions of drug efficacy and safety. The authors review various 3D culture methods, including forced-floating, hanging drop, spinner flask bioreactors, rotating cell culture bioreactors, and the use of matrices and scaffolds. These methods aim to create more physiologically relevant models by mimicking the natural cellular architecture and extracellular matrix (ECM). The article also emphasizes the biological differences between 2D and 3D cultures, such as altered cellular phenotype and sensitivity to drugs. Examples of studies demonstrating the advantages of 3D cultures in drug screening are provided, highlighting their potential to improve the efficiency and success rate of drug development. The authors conclude that incorporating 3D cell spheroids into the drug discovery process can bridge the gap between in vitro and in vivo studies, leading to more effective and less toxic drugs.