Organ-on-chip systems are the emerging in vitro tools to study the effect of chemicals, pharmaceuticals, and nanomaterials on various organs. They combine key functional characteristics of various human organs with specialized microfluidic platforms to evolve systems that mimic the biochemical, metabolic, genetic, and functional characteristics of their target organs. A number of model systems are now available for lung, heart, liver, kidney, heart, brain, gut, bone, and others. More recently, several such systems are being merged together to obtain multiorgan and body-on-chip systems. These systems at present, although primitive, help model the sequential fate of chemicals when exposed to various types of cells and tissues. Using these systems, the toxicity of pharmaceuticals, dyes, proteins, enzymes, and nanomaterials have been studied in a controlled environment. This chapter summarizes some of these organ-on-chip studies, illustrating their key features and benefits. Studies that provide step-by-step fabrication protocols are also highlighted. The chapter concludes with a summary of chemicals and pharmaceuticals that have been studied so far using various organ-on-chip systems.