Applications of antimicrobials in food production and human health have found favor throughout human history. Antibiotic applications in agricultural and human medical arenas have resulted in tremendous increases in food animal production and historically unprecedented gains in human health protection. Successes attributed to widespread antibiotic use have been accompanied by the inadvertent emergence of antibiotic-resistant bacteria. A major problem associated with this emerging resistance is the crossover use of some antibiotics in agricultural settings as well as in the prevention and treatment of human disease. This outcome led to calls to restrict the use of human health-related antibiotics in food animal production. Calls for restricted antibiotic use have heightened existing searches for alternatives to antibiotics that give similar or enhanced production qualities as highly reliable as the antibiotics currently provided to food animals. Agricultural and scientific advances, mainly within the last 100 yr, have given us insights into sources, structures, and actions of materials that have found widespread application in our modern world. The purpose of this presentation is to provide a historic perspective on the search for what are generally known as antibiotics and alternative antimicrobials, probiotics, prebiotics, bacteriophages, bacteriocins, and phytotherapeutics.