The combination of chemo-, radio- and biologic therapies in preparation for hematopoietic stem cell transplantation (HSCT) is referred to as conditioning (or preparative) regimen. As there is no one “standard” regimen, choosing the ideal regimen should take into account numerous factors including: stem cell source (autologous versus allogeneic), diagnosis, disease stage at the time of transplant, prior therapies, and comorbidities. There are few randomized studies comparing regimens and the majority of the data comes from phase 2 or retrospective analysis. Lacking clear-cut evidence supporting the superiority of one conditioning regimen over another, the choice is often based on institutional preference and experience. This chapter will review our current knowledge regarding ablative preparative regimens and some of the controversies that surround the field.