Transplantation of solid organs and cellular grafts has become clinical routine in the last 30 years. However, the requirement for life-long immunosuppression is associated with infections, malignancies and end-organ toxicity. Moreover, the treatment fails to prevent chronic rejection. The induction of donor-specific transplantation tolerance would solve these problems, but has remained an elusive goal. One approach to achieve transplantation tolerance is through hematopoietic chimerism. This review outlines different concepts of hematopoietic chimerism focusing on macrochimerism. Mixed allogeneic chimerism, also known as macrochimerism, is defined as engraftment of hematopoietic stem cells achieved by bone marrow transplantation (BMT). It discusses the advantages and limitations of the BMT as well as approaches to overcome these limitations in the future.