To provide a forum for discussion, the International Conference on Fatigue Science was organized, the first being held in 2002 in Sandhamn, Sweden, and the second in 2005 in Karuizawa, Japan. Subsequently it was decided that the papers presented at the two conferences should be collected. The result is an authoritative guide to recent progress in the molecular and neural mechanisms of fatigue and in the development of the ways to prevent and overcome fatigue and chronic fatigue.