Abstract: Bacteria can exhibit high levels of resistance to one or more environmental stresses such as temperature, osmolarity, radiation, pH, starvation, as well as resistance to noxious chemicals and antibiotics. Yet evolution has not optimized stress resistance in all bacteria to all stresses. Even within a species like Escherichia coli, stress resistance is not constant between strains, suggesting that selection for stress resistance is under counterselection in some environments. The tradeoffs associated with stress resistance in E. coli are due to more than the direct cost of resistance mechanisms. A significant indirect cost is that high stress resistance is associated with a reduced ability to compete for poor growth substrates like acetate or even good substrates like glucose at suboptimal concentrations. High stress resistance also decreases the ability to use inorganic nutrients like phosphate. This tradeoff between self-preservation and nutritional competence, called the SPANC balance, is likely to be the major selective influence in natural populations. Another cost of high stress resistance in E. coli is an elevated mutation rate and the increased generation of deleterious mutations. Directional adaptations in SPANC balance and mutation rate are environment-dependent. The most common variations in SPANC are due to polymorphisms in the levels of global regulators RpoS and ppGpp between different strains. High levels favor stress resistance, and low levels allow better nutrition. The intimate association of RpoS/ppGpp with stress resistance and SPANC balancing influences numerous cellular processes and bacterial properties, including virulence.