Over the past years, important progresses have been made in the field of tissue engineering. Many of the early trials to improve the development of an engineered tissue construct were centered on the concept of seeding cells onto biomaterial scaffold. By means of innovative manufacturing machineries, the conception of a preformed scaffold became possible. Nowadays, several tissue engineering challenges are associated with applying this scaffold technology to one vital organ construct: liver. The development of microscale tissue (“micro-tissue”) constructs to mimic partially the complex structure–function interactions of liver parenchyma have been obtained through the engineering of sophisticated biomaterial scaffolds, liver-cell sources, and in vitro culture techniques. For in vitro applications, micro-tissue constructs are being upgraded into cell-based assays for testing acute, chronic and idiosyncratic toxicities of drugs or pathogens. The present chapter will focus on the biomaterials currently used for the development of in vitro liver constructs as well as the description of the microfluidic-based models that show great promise for liver regenerative medicine approaches.