Autocrine/paracrine regulatory mechanisms are believed to play a role in the pathophysiology of several hematologic malignancies. Evidence is accumulating that various growth factors, cytokines, and chemokines are expressed and secreted by normal early and differentiated hematopoietic cells and thus could also regulate normal hematopoiesis in an autocrine/paracrine manner. In this review we summarize recent advances in identification and understanding of the role of autocrine/paracrine axes in the growth of both malignant and normal human hematopoietic cells. Better understanding of intercellular crosstalk operating in normal and pathological states and the mechanisms regulating synthesis of these endogenously produced factors (potential targets for various pharmacological approaches) may allow us to improve antileukemia treatments, undertake more efficient ex vivo stem cell expansion, and develop other therapeutic strategies.