Our relationship with the colonic bacterial flora has long been viewed as benign, but recent studies suggest that this symbiosis has risks as well as benefits. This relationship requires that the host not only provide a supportive environment for the symbiotic bacteria, but also actively maintain intact mechanisms for properly managing the physiologic stresses that are closely associated with the symbiont's essential survival functions. Failure to do so breaches the host-symbiont contract, and can result in serious effects on the health of the host. Recent investigations that employ several knockout mouse models reveal the consequences of genetic deficiency in the host regarding these mechanisms, and the latent, pro-inflammatory, tumorigenic nature of normal bacterial flora. Further study of the interactions between normal bacterial flora and hosts could shed light on the etiologies and pathogenesis of inflammatory diseases and related cancers, with implications for human health.