Post-activation potentiation (PAP) is induced by a voluntary conditioning contraction (CC), performed typically at a maximal or near-maximal intensity, and has consistently been shown to increase both peak force and rate of force development during subsequent twitch contractions. The proposed mechanisms underlying PAP are associated with phosphorylation of myosin regulatory light chains, increased recruitment of higher order motor units, and a possible change in pennation angle. If PAP could be induced by a CC in humans, and utilized during a subsequent explosive activity (e.g. jump or sprint), it could potentially enhance mechanical power and thus performance and/or the training stimulus of that activity. However, the CC might also induce fatigue, and it is the balance between PAP and fatigue that will determine the net effect on performance of a subsequent explosive activity. The PAP-fatigue relationship is affected by several variables including CC volume and intensity, recovery period following the CC, type of CC, type of subsequent activity, and subject characteristics. These variables have not been standardized across past research, and as a result, evidence of the effects of CC on performance of subsequent explosive activities is equivocal. In order to better inform and direct future research on this topic, this article will highlight and discuss the key variables that may be responsible for the contrasting results observed in the current literature. Future research should aim to better understand the effect of different conditions on the interaction between PAP and fatigue, with an aim of establishing the specific application (if any) of PAP to sport.