Four macrominerals have the distinction of being involved in the "downer cow" syndrome, which is, unfortunately, often associated with parturition in cows. Inadequate blood calcium (Ca), phosphorus (P), magnesium (Mg), or potassium (K) concentrations can cause a cow to lose the ability to rise to her feet because these minerals are necessary for nerve and muscle function. Less severe disturbances in blood concentrations of these minerals can cause reduced feed intake, poor rumen and intestine motility, poor productivity, and increased susceptibility to other metabolic and infectious disease. Mechanisms for maintaining blood Ca, P, Mg, and K concentrations perform efficiently most of the time, but occasionally these homeostatic mechanisms fail and metabolic diseases such as milk fever occur. Understanding how and why these mechanisms fail may allow the practitioner to develop strategies to avoid these disorders.