Hematopoiesis is a process in which the Hematopoietic stem cells (HSC's) differentiate to give rise to all lineages of blood cells. In normal adults, HSC's reside in the bone marrow (BM) and their cell niche (microenvironment) in the BM is well-studied in the literature. However, when the BM microenvironment is stressed or diseased, Hematopoiesis takes place in other hematopoietic organs. One of the primary hemic organs is the spleen, yet the mechanisms and microenvironments of the spleen that regulate hematopoiesis and HSC's are not well investigated. By synthesizing articles from the literature, and comparing the spleen hematopoiesis niche to the bone marrow niche, this review will shed light on some of the factors and aspects that mediate hematopoiesis in the spleen microenvironments. It is important to understand how hematopoiesis operates in the spleen as it will provide insights into understanding hematological diseases and some prospective treatments.