The loss or failure of an organ or tissue is one of the most frequent, devastating, and costly problems in healthcare. Current treatment modalities include transplantation of organs, surgical reconstruction, use of mechanical devices, or supplementation of metabolic products. A new field, tissue engineering, applies the principles and methods of engineering, material science, and cell and molecular biology toward the development of viable substitutes which restore, maintain, or improve the function of human tissues. In this review, we outline the opportunities and challenges of this emerging interdisciplinary field and its attempts to provide solutions to tissue creation and repair. Within this context, we present our experience using the basic tools of tissue engineering to guide regeneration of diverse tissues that include the liver, small intestine, cardiovascular structures, nerve, and cartilage. And in addition, we discuss the necessity of finding new strategies to achieve vascularization of complex tissues for transplant and present our approaches utilizing MicroElectroMechanical Systems (MEMS) technology and three-dimensional printing.