For much of the 20th century, lactate (La^-) was largely considered a deadend waste product of glycolysis due to hypoxia, the primary cause of the O₂ debt following exercise, a major cause of muscle fatigue, and a key factor in acidosis-induced tissue damage. Since the 1970s, a "lactate revolution" has occurred. Presently, we are in the midst of a lactate shuttle era; the La^- paradigm has shifted. It now appears that increased La^- production and [La^-] as a result of anoxia or dysoxia are often the exception rather than the rule. Lactic acidosis is being re-evaluated as a factor in muscle fatigue. Lactate is an important intermediate in the process of wound repair and regeneration. The origin of elevated [La^-] in injury and sepsis is being re-investigated. There is essentially unanimous experimental support for a cell-to-cell lactate shuttle, along with mounting evidence for astrocyte-neuron, lactate-alanine, peroxisomal, and spermatogenic lactate shuttles. The bulk of the evidence suggests that La^- is an important intermediary in numerous metabolic processes, a particularly mobile fuel for aerobic metabolism, and perhaps a mediator of redox state among various compartments both within and between cells. La^- can no longer be considered the usual suspect for metabolic "crimes", but is instead a central player in cellular, regional, and whole body metabolism. Overall, the cell-to-cell lactate shuttle has expanded far beyond its initial conception as an explanation for muscle and exercise metabolism to now subsume all of the other shuttles as a grand description of the role(s) of La^- in numerous metabolic processes and pathways.