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The barriers to HLA-mismatched or haploidentical hematopoietic stem cell transplantation (HSCT), namely GvHD and graft failure, have been overcome with novel transplant platforms. Post-transplant Cyclophosphamide (PTCy) is widely available, feasible and easy to implement. TCRαβ T and B cell depletion comes with consistent GvHD preventive benefits irrespective of age and indication. Naive T-cell depletion helps prevention of severe viral reactivations. The Beijing protocol shows promising outcomes in patients with poor remission status at the time of transplantation. For children, the toxicities and late outcomes related to these transplants are truly relevant as they suffer the most in the long run from transplant-related toxicities, especially chronic GvHD. While comparing the outcomes of different Haplo-HSCT approaches, one must understand the transplant immunobiology and factors affecting the transplant outcomes. Leukemia remission status at the time of conditioning is a consistent factor affecting the transplant outcomes using any of these platforms. Prospective comparison of these platforms lacks in a homogenous population; however, the evidence is growing, and this review highlights the areas of research gaps.