Our immune system functions to protect us from a myriad of potentially harmful threats, external and internal; most often with an efficiency that goes unnoticed. It is only when an invading organism or a rogue cell gets the upper hand, that we notice the manifestation of symptoms. It is these challenges to the immune system that results in the majority of hospital and physician visits- often resulting in a prescription antibiotic or analgesic. Once in a generation, a vast global pandemic pits an organism (such as the SARS-CoV-2 virus) against our collective immune systems- often revealing underlying vulnerabilities of devastating consequences. Not only do such challenges reveal the importance of maintaining metabolic reserve capacity (in all tissues), they also give an opportunity for people to think about a more comprehensive immune-building strategy. In this short monograph we aim to do two things: lay out the core principles for maintaining or building a strong immune defense against any present or future challenge, and, in keeping with the primary theme of these monographs, overview the evidence for key immune-enhancing supplement ingredients. While the diversity of remedies and research modalities make it difficult to capture all the historical and emerging clinical approaches, this overview will discuss some of the most widely researched botanicals and nutraceutical immunomodulators, with a focus on published clinical trials and potential mechanisms from in vitro and animal research.