The causal relationship between iron deficiency and physical work capacity is evaluated through a systematic review of the research literature, including animal and human studies. Iron deficiency was examined along a continuum from severe iron-deficiency anemia (SIDA) to moderate iron-deficiency anemia (MIDA) to iron deficiency without anemia (IDNA). Work capacity was assessed by aerobic capacity, endurance, energetic efficiency, voluntary activity and work productivity. The 29 research reports examined demonstrated a strong causal effect of SIDA and MIDA on aerobic capacity in animals and humans. The presumed mechanism for this effect is the reduced oxygen transport associated with anemia; tissue iron deficiency may also play a role through reduced cellular oxidative capacity. Endurance capacity was also compromised in SIDA and MIDA, but the strong mediating effects of poor cellular oxidative capacity observed in animals have not been demonstrated in humans. Energetic efficiency was affected at all levels of iron deficiency in humans, in the laboratory and the field. The reduced work productivity observed in field studies is likely due to anemia and reduced oxygen transport. The social and economic consequences of iron-deficiency anemia (IDA) and IDNA have yet to be elucidated. The biological mechanisms for the effect of IDA on work capacity are sufficiently strong to justify interventions to improve iron status as a means of enhancing human capital. This may also extend to the segment of the population experiencing IDNA in whom the effects on work capacity may be more subtle, but the number of individuals thus affected may be considerably more than those experiencing IDA.