Accumulation of muscle lactate and lowering of muscle pH during intense exercise do not per se cause fatigue during exercise, but it appears that they contribute to fatigue development in humans. This may be related to lowered muscle pH causing greater release of K+ from the contracting muscles and sensation of fatigue. Training elevates the capacity to release lactate and H+ as well as to buffer H+, probably contributing to the enhanced performance during intense exercise after a training period. In this review, we discuss the role of lactate and H+ for intense exercise performance in humans.