The immune system offers sophisticated molecular solutions to avoid the threat of infections and cancer. Based on these molecular, novel therapeutic concepts can be developed and adjusted. Therapeutic manipulation of innate immunity therefore offers an alternative to failing antibiotics and cancer therapies but is underexplored, due to issues of specificity. We have identified novel, specific molecular activation nodes and effector molecules that distinguish protective from destructive effects of innate immune activation in infections and cancer. This approach can design therapeutics, to selectively attenuate destructive innate immune responses to infection without jeopardizing the antibacterial defense. We also explore natural molecules of the innate immune system for antibacterial effects and in cancer therapy. These studies are essential, In view of the global increase in drug-resistant bacteria and cancer-associated mortality, especially in the aging population.