In recent years solid organ transplantation has been rapidly developed as a therapeutic intervention that is life-saving and greatly contributes to a better quality of life in organ recipients. The rapid development has been made possible because of a drastic expansion in the immunosuppressive repertoire. Unfortunately, the side effects of these drugs can be severe, which is one of the reasons that life expectancy of transplant patients still significantly falls short of that of the general population. In this review manuscript we will discuss current and future immunosuppressive strategies that are employed in solid organ transplantation. Expanding our understanding of the human immune system will hopefully provide us with newer, smarter drugs that promote immunotolerance without the side effects observed today.