Splenectomy represents the first choice for treatment of spontaneous splenic rupture, abscesses, cysts, tumours, and an alternative for control of hereditary, autoimmune, and myeloproliferative disorders. However, its relative indications have been reviewed for better understanding of both the primary affections and of splenectomy per se, particularly with regard to the immune system. The emergence of minimally invasive surgery, the possibility of splenic preservation, and availability of biological therapy has shown that the procedure has often been referred to as salvage therapy upon failure of other therapeutic propositions. On the other hand, patients have their general health status compromised by the underlying disease, by the use corticosteroids or biologic therapy, immunosuppressed, coagulation disorders, which contribute to the incidence of postoperative complications, such as infections, bleeding and venous thrombosis. Therefore, this scenario favours higher morbidity and mortality rates than those of other intra-abdominal surgical procedures. Thus, this review has the primary and comprehensive objective of purpose the best moment for splenectomy, when surgeons can interfere in the natural course of the disease increasing patients’ quality of life and survival. In short, it is desired that the surgeon has complete knowledge of the profound physiological changes imposed on the host. In addition, to distinguish when it is curative and mandatory from when it must be put on hold due to other non-operative treatments with similar outcomes and, lastly, when it is not recommended for not aggregating survival.