The evolution and spread of antibiotic resistance depends on the antibiotic pressure exerted in the microbial environment. Selective effects occur in selective compartments, where particular antibiotic concentrations result in a differential growth rate of resistant bacterial variants. This may happen even at very low antibiotic concentrations able to select low-level-resistant bacteria. When more than one antibiotic is present in the environment, the multiple and fluctuating pressure produces the selection of bacterial variants that use multiple or multipurpose mechanisms or optimize a single mechanism of resistance to survive under the variable environmental conditions. Host factors such as immunity contribute to the selective process. Antibiotics themselves may promote bacterial diversity, either mediated by the random drift effect or triggering the increase of mutational events under bacterial stress. Analysis of selective environment-related antibiotic-host-bacteria interactions is essential to understanding the biology of antibiotic resistance.