In recent years, ever-increasing scientific knowledge and modern high-tech advancements in micro- and nano-scales fabrication technologies have impacted significantly on various scientific fields. A micro-level approach so-called “microfluidic technology” has rapidly evolved as a powerful tool for numerous applications with special reference to bioengineering and biomedical engineering research. Therefore, a transformative effect has been felt, for instance, in biological sample handling, analyte sensing cell-based assay, tissue engineering, molecular diagnostics, and drug screening, etc. Besides such huge multi-functional potentialities, microfluidic technology also offers the opportunity to mimic different organs to address the complexity of animal-based testing models effectively. The combination of fluid physics along with three-dimensional (3-D) cell compartmentalization has sustained popularity as organ-on-a-chip. In this context, simple humanoid model systems which are important for a wide range of research fields rely on the development of a microfluidic system. The basic idea is to provide an artificial testing subject that resembles the human body in every aspect. For instance, drug testing in the pharma industry is crucial to assure proper function. Development of microfluidic-based technology bridges the gap between in vitro and in vivo models offering new approaches to research in medicine, biology, and pharmacology, among others. This is also because microfluidic-based 3-D niche has enormous potential to accommodate cells/tissues to create a physiologically relevant environment, thus, bridge/fill in the gap between extensively studied animal models and human-based clinical trials. This review highlights principles, fabrication techniques, and recent progress of organs-on-chip research. Herein, we also point out some opportunities for microfluidic technology in the future research which is still infancy to accurately design, address and mimic the in vivo niche.