B. anthracis virulence is the sum of the contributions of factors involved in toxicity, growth and persistence in the host. Recent data has revealed that the interactions between B. anthracis and macrophage is central to the B. anthracis pathogenesis. This review presents and describes tactics by which B. anthracis not only overcomes and avoids macrophages but also perverts the host defense immune system and defense-related products to its advantage. The understanding of the complex network of such interactions is likely to allow new therapeutic and preventative strategies to be developed.