Organs-on-chips are microengineered models of human organs that offer new opportunities for preclinical drug discovery. These models, which replicate the complex structure, microenvironment, and physiological functions of human organs, can provide more accurate predictions of drug efficacy and safety than traditional models. They are particularly useful for target identification and validation, target-based screening, and phenotypic screening. The pharmaceutical industry faces challenges due to rising costs and declining efficiency in drug development, and organs-on-chips could help address these issues by providing more reliable preclinical data. Organs-on-chips use microfabrication and microfluidics to control the cellular microenvironment with high precision, enabling the simulation of complex biological processes. They can recapitulate the structural and functional complexity of human organs such as the liver, heart, lung, intestine, kidney, brain, and bone. For example, a lung-on-a-chip model can simulate the alveolar–capillary barrier and has been used to study the effects of physiological breathing on inflammatory responses. This model has also been used to study the development and progression of pulmonary oedema induced by the anticancer drug interleukin-2 (IL-2). Compared to conventional models, organs-on-chips offer several advantages, including better simulation of drug delivery and penetration, more accurate representation of complex interactions between different cell types, and the ability to control mechanical cues such as fluid shear stress, tension, compression, and torque. They also provide real-time visualization and quantitative analysis of biological processes, which is not possible with animal models. Additionally, organs-on-chips can reduce the use of costly reagents and may be used earlier in the drug discovery pipeline than animal models. Organs-on-chips have been used to identify and validate the efficacy, safety, and druggability of potential targets. For example, a microengineered model of vasculature was used to study chemokine-mediated interactions between circulating breast cancer cells and the microvascular endothelium. This model revealed that the vascular endothelium plays a critical role in the metastatic behaviour of circulating tumour cells. Another study used a microengineered model of liver cancer to investigate the anticancer effects of artemisinin, an antimalarial drug. Organs-on-chips are also being used for drug screening, including efficacy and toxicity screening. They can provide more reliable predictions of drug efficacy and toxicity than traditional models, and have been used to study the effects of drugs on various organs and tissues. For example, a liver-on-a-chip model has been used to study the metabolism of drugs and their toxic effects. A heart-on-a-chip model has been used to study the effects of drugs on cardiac function. Phenotypic screening using organs-on-chips can help identify drugs that ameliorate disease phenotypes without initial concern for the molecular mechanisms of action. This approach has been used to investigate approved drugs or drugs that failed to meetOrgans-on-chips are microengineered models of human organs that offer new opportunities for preclinical drug discovery. These models, which replicate the complex structure, microenvironment, and physiological functions of human organs, can provide more accurate predictions of drug efficacy and safety than traditional models. They are particularly useful for target identification and validation, target-based screening, and phenotypic screening. The pharmaceutical industry faces challenges due to rising costs and declining efficiency in drug development, and organs-on-chips could help address these issues by providing more reliable preclinical data. Organs-on-chips use microfabrication and microfluidics to control the cellular microenvironment with high precision, enabling the simulation of complex biological processes. They can recapitulate the structural and functional complexity of human organs such as the liver, heart, lung, intestine, kidney, brain, and bone. For example, a lung-on-a-chip model can simulate the alveolar–capillary barrier and has been used to study the effects of physiological breathing on inflammatory responses. This model has also been used to study the development and progression of pulmonary oedema induced by the anticancer drug interleukin-2 (IL-2). Compared to conventional models, organs-on-chips offer several advantages, including better simulation of drug delivery and penetration, more accurate representation of complex interactions between different cell types, and the ability to control mechanical cues such as fluid shear stress, tension, compression, and torque. They also provide real-time visualization and quantitative analysis of biological processes, which is not possible with animal models. Additionally, organs-on-chips can reduce the use of costly reagents and may be used earlier in the drug discovery pipeline than animal models. Organs-on-chips have been used to identify and validate the efficacy, safety, and druggability of potential targets. For example, a microengineered model of vasculature was used to study chemokine-mediated interactions between circulating breast cancer cells and the microvascular endothelium. This model revealed that the vascular endothelium plays a critical role in the metastatic behaviour of circulating tumour cells. Another study used a microengineered model of liver cancer to investigate the anticancer effects of artemisinin, an antimalarial drug. Organs-on-chips are also being used for drug screening, including efficacy and toxicity screening. They can provide more reliable predictions of drug efficacy and toxicity than traditional models, and have been used to study the effects of drugs on various organs and tissues. For example, a liver-on-a-chip model has been used to study the metabolism of drugs and their toxic effects. A heart-on-a-chip model has been used to study the effects of drugs on cardiac function. Phenotypic screening using organs-on-chips can help identify drugs that ameliorate disease phenotypes without initial concern for the molecular mechanisms of action. This approach has been used to investigate approved drugs or drugs that failed to meet