Organ-on-a-chip systems, also referred to as microphysiological systems (MPS), represent an advance in bioengineering microsystems designed to mimic key aspects of human organ physiology and function. Drawing inspiration from the intricate and hierarchical architecture of the human body, these innovative platforms have emerged as invaluable in vitro tools with wide-ranging applications in drug discovery and development, as well as in enhancing our understanding of disease physiology. The facility to replicate human tissues within physiologically relevant three-dimensional multicellular environments empowers organ-on-a-chip systems with versatility throughout different stages of the drug development process. Moreover, these systems can be tailored to mimic specific disease states, facilitating the investigation of disease progression, drug responses, and potential therapeutic interventions. In particular, they can demonstrate, in early-phase pre-clinical studies, the safety and toxicity profiles of potential therapeutic compounds. Furthermore, they play a pivotal role in the in vitro evaluation of drug efficacy and the modeling of human diseases. One of the most promising prospects of organ-on-a-chip technology is to simulate the pathophysiology of specific subpopulations and even individual patients, thereby being used in personalized medicine. By mimicking the physiological responses of diverse patient groups, these systems hold the promise of revolutionizing therapeutic strategies, guiding them towards tailored intervention to the unique needs of each patient. This review presents the development status and evolution of microfluidic platforms that have facilitated the transition from cells to organs recreated on chips and some of the opportunities and applications offered by organ-on-a-chip technology. Additionally, the current potential and future perspectives of these microphysiological systems and the challenges this technology still faces are discussed.