Splenectomy is a well-established therapeutic intervention in the management of various hematologic disorders and several solid organ tumors. In many of the hematologic disorders, the spleen plays a pathologic role in terms of hypersplenism or symptomatic splenomegaly. Hypersplenism is when the spleen becomes overactive resulting in the removal of certain cell lines from the peripheral blood. This leads to various cytopenias that are usually symptomatic. In certain solid organ tumors (e.g. gastric and pancreatic) the spleen is removed to obtain adequate surgical margins, exposure or when the splenic vascular supply is removed with the specimen. Since the introduction of splenectomy into surgical practice, the morbidity/mortality from this procedure has changed dramatically secondary to gaining surgical experience and advances in surgical techniques. Splenic preservation is preferred during distal pancreatectomy, but not at the cost of oncologic cure. Splenectomy for proximal gastric cancer should be done if there is extension of tumor into the spleen, pancreas or macroscopic nodal metastases to the splenic hilum. Splenectomy for ITP is indicated for failure of medical therapy and provides a permanent cure in the majority of patients. Laparoscopic splenectomy is the surgical treatment of choice in these patients. Splenectomy is curative in the treatment of patients with hereditary spherocytosis. Laparoscopic splenectomy is safe in this patient population. Consider the need for laparoscopic cholecystectomy during the same procedure if they have gallstones. Splenectomy is a life-saving procedure in sickle cell patients during an acute sequestration crisis. Splenectomy is indicated in patients with Myeloproliferative disorders (CML, AML, CMML, ET, PV and MM) with symptomatic splenomegaly and cytopenias. Splenectomy is effective in treating patients with leukemia (CLL) or lymphoma (NHL) with cytopenias- resulting in a decrease in their transfusion requirements. Laparoscopic splenectomy is as safe and effective as open splenectomy even in cases of massive splenomegaly.