Fatigue is of major concern in aviation because of its link with severe crashes and the fatigue effects of work scheduling. The safety monitoring bodies in aviation, however, impose restrictions on scheduling of aircrew in order to safeguard against severe fatigue. This chapter focuses on how aircrew scheduling affects fatigue in relation to present-day flight time limitations (FTL). The impression from a series of recent studies of long-and short-haul operations is that encroachment on window of circadian low (WOCL; 02:00 to 05:59 hours) is the key factor, together with early morning flights. Duration of the flight duty period is associated with increased fatigue under some circumstances. Number of sectors (“flights”) seems not to be a decisive factor in and of itself. Shortened sleep before flights increases in-flight fatigue. Accumulated flight duty time during the week is not associated with fatigue (within current FTL restrictions). Aircrew seem good at retrospectively identifying causes of reduced fatigue. It was concluded that number of sectors may receive too much emphasis in flight time limitations, whereas encroachment on the WOCL and pre-flight sleep receive too little emphasis, and duty time deserves intermediate attention.