This study will focus on the Histatins (Hst), a family of saliva proteins that act as a first line of defence of our innate immune system and possess antiviral/antimicrobial/antifungal properties. Of specific interest are Histatin 1 (Hst1), Histatin 3 (Hst3), and Histatin 5 (Hst5). These peptides contain 38, 32, and 24 amino acids, respectively, of which the 22 first amino acids in the primary sequence are close to identical, barring a few deviations in Hst1. Here, we aim to understand from a biophysics perspective why Hst5 has a greater killing efficacy for fungi and microbes and less for a virus such as Influenza A (IAV). In contrast, the opposite relationship prevails for Hst1 and Hst3. The aim is to achieve a molecular understanding of the underlying physics and the structure-function relationship by utilizing the toolbox we have developed for more than a decade of research for Hst5, combining computer simulations and experiments.