Tissue engineering is a multifaceted technology developed with a purpose of regenerating complex tissues and organs. Cartilage regeneration continues to challenge engineers and a new wave of efforts focus on developing strategies that provide sustained stimulation to cells by growth factors and other biological molecules to promote their differentiation into chondrocytes. Though significant research is dedicated to developing controlled release systems that deliver growth factors directly, a simpler approach to resolving this dilemma involves converting cells into protein producing factories. This is done through gene delivery. Gene Therapy studies published for articular diseases such as rheumatoid and osteoarthritis provide valuable information regarding different types of cells, gene delivery vectors and genes that can potentially be used to regenerate cartilage. Tissue engineering approaches provide the opportunity to combine two or more strategies used for Gene Therapy thus far and create a cohesive system that addresses both cartilage degeneration and synthesis simultaneously. Adopting gene transfer techniques for tissue engineering is a relatively novel approach, as non-viral gene delivery vectors are continually optimized for therapeutic purposes, and reservations about viral vectors have increasingly dampened their appeal. However, every element involved in gene transfection (i.e., the cell, vector and gene) is a variable which decides the physiological and biomechanical properties of the cartilage produced, and significant work still needs to be done in understanding the contribution of each of these factors to cartilage regeneration.