The dominant effect of the microenvironment on the prognosis of a cancer probably reflects the importance of the immune cells in the biology and pathogenesis of hematologic cancers. Such observations lend support to the notion that the growth of some hematologic cancers is not always autonomous. A good example is the gastric mucosa-associated lymphoid tissue lymphomas associated with infection by the Helicobacter pylori bacterium; many patients with this lymphoma can be cured in their early stages by use of antibiotics which eradicate the infection. In some patients with B-cell chronic lymphocytic leukemia (B-CLL), there is evidence that suggests activation by antigens, which are likely to play a decisive role in the pathogenesis in these patients. If the critical components of the microenvironment in B-CLL or follicular lymphoma can be identified, we can anticipate new treatment options.