The 2010 FIFA World Cup will be held in South Africa in June/July 2010. This is the largest international sports event ever to be held in this country. At this time 32 international football teams, with their management and supporters, will travel to South Africa. These players and visitors will be exposed to changes in time zones (those travelling from continents in the East and West) as well as different environmental conditions. In particular, for the players, the achievement of peak sporting performance during this event is most important. It is well established that, in order to achieve peak exercise performance, many variables need to be optimised. These variables include physical and mental training, rest, nutrition, team dynamics and tactics. However, adjustments to differences in time zones as well as environmental factors on and around the playing field can also have a significant impact on exercise performance. In this review, the potential effects of “jet lag”, as well as several important environmental conditions, on exercise performance will be discussed. The climatic, atmospheric and weather conditions that are likely to be prevalent in each of the South African host cities at the time of the 2010 FIFA World Cup will be reviewed. Finally, practical recommendations to deal with the effects of jet lag, as well as guidelines to optimise performance under different environmental conditions that are expected during the 2010 FIFA World Cup, will be provided.