Hospitals worldwide have lately reported a worrying increase in the number of isolated drug-resistant pathogenic microbes. This has to some extent fueled at least academic interest in design and development of new lead components for novel drug design. Much of this interest has been focused on antimicrobial peptides and peptides in general, primarily due to their natural occurrence and low toxicity. However, issues have been raised regarding the stability of peptide therapeutics for systemic use. The focus of this chapter is assays for measuring peptide stability in the presence of serum, both in vitro and in vivo.