Microfluidics aims to design systems based on microchannels in which small volumes of fluids are used to achieve different applications in fuel cells, optics, life sciences, among others. Microfluidic devices are commonly used in cell biological research and especially in tissue engineering with multiple applications. In this chapter we will focus on a specific application, such as 3D cell culture to model and simulate different regenerative processes associated with disease, damage or aging. In addition, these microdevices are also an excellent system for drug testing and modeling different diseases and their corresponding therapeutic treatments. For tissue engineering, this technology has several advantages over traditional 2D and 3D cell culture methods, such as spatiotemporal controllability, fluid flow control, physiological mimicry of living tissue, and high-throughput analysis with smaller sample sizes. In addition, microdevices do not have the cost and ethical issues of animal experimentation. Therefore, this chapter will first review some of the techniques and materials used in the fabrication of microfluidic devices. Then, it will show different types of 3D cell cultures that can be developed in these chips by controlling different factors of the microenvironment. Finally, recent advances in microfluidic-based tissue engineering and some examples of successful studies in organ-on-a-chip and cancer applications are discussed.