Emerging companies are the lifeblood of biotech innovation. Over time, the share of FDA-approved therapies originating from small and mid-sized biotech companies has grown steadily, now accounting for over half. These companies take great risks, operate with lean resources, and focus deeply on breakthrough science; however, they possess only a fraction of the financial and organizational resources of large pharmaceutical companies. While the entire industry is facing existential threats from current policies and the macroeconomic environment, it is precisely these crises that place earlier stage companies at greatest risk. In addition to decreasing early-stage institutional funding, looming cuts to NIH, NSF, and other public funding streams disproportionately affect academic research and early-stage ventures. In this discussion, seasoned early- and mid-stage CEOs and serial entrepreneurs share their views on the resilience and resourcefulness of small companies, the role of groups such as the Biotech CEO Sisterhood in leveraging collective wisdom and networks to increase chances of success, key advice for current and aspiring small company CEOs, and more.