Myeloablative therapy followed by autologous hematopoietic stem cell (HSC) transplantation is a therapeutic option proposed for a variety of hematological and non-hematological diseases. However, although mortality due to this procedure is steadily decreasing, patients are still exposed to the risk of a number of complications negatively affecting their expectancy or quality of life. Adverse events due to HSC harvesting are rare and generally reversible. The early post-transplant complications include infections, mucositis, hepatic veno-occlusive disease and various acute organ toxicities. Immune derangement is a leading cause of most late events, such as viral or fungal infections, auto-immune manifestations and secondary neoplasms, of which secondary AML/MDS are the most commonly reported. In line with the favoured pathogenetic explanation, neoplastic clones previously established during conventional treatment are harvested and reinfused at the time of autografting. Other late effects are single organ dysfunction due to the underlying disease and treatment toxicities combined with infectious and post-infectious phenomena. The lungs, heart, CNS and reproductive system are the most investigated targets, but no clinical patterns have been identified as specific for autografting.