The hematopoietic cell transplantation practice has changed significantly over the years. More than 1500 centers around the globe are offering transplant for different types of diseases. This growth was driven by improving the efficacy and the safety of the procedure and the ability to use alternate donors. These improvements made the procedure feasible in virtually all patients in need for it. With the availability of novel therapies and targeted agents, we may be witnessing a new transplant-era. These agents may help to circumvent some of the remaining limitations of the procedure and open the doors for new indications. Herein, we review historical transplant milestones, the accomplishments that led to the modern transplant practice and we discuss the idea of minimal-intensity conditioning and the possibility to adopt chemotherapy and radiation-free preparative regimens in the near future.