The use of alternative hematopoietic stem cell (HSC) donors has been witnessing important progress, mainly due to: (i) better HLA matching at the allelic level between donor and recipient in unrelated HSC transplantation (HSCT) translating into better patient outcome; (ii) better donor choice and patient selection in unrelated, often HLA-mismatched, cord blood transplantation and (iii) new strategies of adoptive cell therapy aimed at improving the results of T-cell-depleted haploidentical HSCT from a relative. Currently, it is possible to find an HSC donor for virtually almost all children with an indication to receive allogeneic HSCT and lacking an HLA-identical sibling. Each of the three options of HSCT from alternative donors has advantages and limitations. Therefore, any physician has to carefully evaluate, for each single pediatric patient in need of an allograft, all the possible alternatives to choose the best HSC donor, taking into account type of disease to be treated, urgency of transplantation, donor characteristics and center's experience. This review will analyze in detail the advantages and limitations of each of the three options of alternative donor HSCT and the main criteria to be used for choosing the most suitable donor for pediatric patients lacking an HLA-identical sibling.