As the first line of defense, the innate immunity kick starts all downstream immunity. Therefore, all therapeutics that requires adaptive immunity including cancer immunotherapy cannot succeed without appropriate and specific activation of the innate immunity against the real threat. On the flip side, the innate immunity does not react to specific threat, but rather molecular patterns that assemble pathogens and can react to our self DNA and RNA inappropriately during trauma, aging, autoimmune syndromes, or after an infection. The innate immunity is a fertile ground for therapeutic development both for its activation and inhibition because of its relevance in all these aforementioned physiologies. In addition, the innate immunity is poised for small molecule drug development because the pathways all recognize small molecule patterns. The challenges this meeting is hoping to address are how to achieve self vs. non-self-specificity in agonists development and understanding the master regulators/drug targets in antagonists development. We therefore propose that this meeting should first and foremost be molecular and mechanistic. Secondly, we discuss the relevance of each pathway in disease settings with an emphasis on their therapeutic relevance. Finally, we will hear hot off the press reports on how the first-generation drugs targeting nucleic acid sensing pathways are doing in clinical trials from our industry and clinician presenters. We also propose joint talks with the T cell meeting that specifically elucidate how innate immune pathways cross talk with intended or unintended T cell activation. This meeting will bring biochemists, molecular biologists, clinicians, and drug developers under one roof to facilitate clinical translation of this field.