Mastitis is an inflammation of the mammary gland most often caused by a bacterial intramammary infection. Antimicrobials are often used for mastitis treatment and control, and dairy cattle receive more antimicrobial therapy for mastitis than for all other dairy cattle diseases combined. Mastitis can be categorized based on the severity of the inflammatory response as subclinical, having no overt clinical signs, or clinical, having overt changes in the milk, mammary gland, and/or cow. Clinical mastitis is divided into mild (overt changes in the milk), moderate (overt changes in the milk and udder inflammation such as redness, heat, pain, and swelling), or severe (overt changes in the milk, mammary gland, and systemic signs in the cow). Treatment decisions will not only be dictated by the severity of the disease, but also by the inciting agent and the predicted outcome of therapy based on empirical or scientific evidence. A common strategy is to try to clear the bacterial invaders with antibiotics in the hope of returning the mammary gland to normal function, but this strategy may not always be warranted or effective and thus understanding basic principles of therapy are critical. Challenges faced by the dairy industry include public concerns about cattle welfare and antimicrobial drug use and resistance. These concerns are driving policy aimed at reducing or eliminating certain types of antimicrobial use in food-producing animals because of real or perceived concerns about resistance in pathogens of human health importance. It is clear that antimicrobial use in food-producing animals is an evolving situation and one that likely will be more restrictive in the future. Prudent use of antimicrobial drugs, i.e., only applying antimicrobials where there are clearly demonstrated production and animal welfare benefits is a logical step in potentially reducing antimicrobial use on farms while preserving the ability to treat disease and optimize animal well-being. The future of mastitis treatment lies in optimizing management practices that promote animal health and reduce disease incidence while developing novel intervention strategies aimed at reducing antimicrobial usage.