Bacterial resistance to multiple antibiotics is a serious and emerging threat. Several measures have been proposed to curb this growing trend. These include prescribing restrictions, education, and infection control that target transmission, among several others. Antibiotic cycling has been a subject of debate, and although many investigators have studied the utility of antibiotic cycling with the help of theoretical models or as part of clinical investigations, several areas remain undefined and unclear. This review summarizes the available information on antibiotic heterogeneity (antibiotic cycling, antibiotic mixing, and other types of antibiotic protocols) with a critical analysis of the published studies.