The quest for bacterial survival is exemplified by spores formed by some Firmicutes members. They turn up everywhere one looks, and their ubiquity reflects adaptations to the stresses bacteria face. Spores are impactful in public health, food safety, and biowarfare. Heat resistance is the hallmark of spores and is countered principally by a mineralized gel-like protoplast, termed the spore core, with reduced water which minimizes macromolecular movement/denaturation/aggregation. Dry heat, however, introduces mutations into spore DNA. Spores have countermeasures to extreme conditions that are multifactorial, but the fact that spore DNA is in a crystalline-like nucleoid in the spore core, likely due to DNA saturation with small acid-soluble spore proteins (SASPs), suggests that reduced macromolecular motion is also critical in spore dry heat resistance. SASPs are also central in the radiation resistance characteristic of spores, where the contributions of four spore features—SASP; Ca2+, with pyridine-2,6-dicarboxylic acid (CaDPA); photoproduct lyase; and low water content—minimize DNA damage. Notably, the spore environment steers UV photochemistry toward a product that germinated spores can repair without significant mutagenesis. This resistance extends to chemicals and macromolecules that could damage spores. Macromolecules are excluded by the spore coat which impedes the passage of moieties of ≥10 kDa. Additionally, damaging chemicals may be degraded or neutralized by coat enzymes/proteins. However, the principal protective mechanism here is the inner membrane, a compressed structure lacking lipid fluidity and presenting a barrier to the diffusion of chemicals into the spore core; SASP saturation of DNA also protects against genotoxic chemicals. Spores are also resistant to other stresses, including high pressure and abrasion. Regardless, overarching mechanisms associated with resistance seem to revolve around reduced molecular motion, a fine balance between rigidity and flexibility, and perhaps efficient repair.