Macrophage migration inhibitory factor (MIF) has an amazing history of rediscoveries and controversies surroundings its true biological function. It has been classified as a powerful cytokine capable of inducing tumour necrosis factor (TNF)-alpha, IL-1beta, IL-6, IL-8, PGE2 along with its ability to override glucocorticoid activity in relation to TNF-alpha release from monocytes. However, our recent study has failed to reproduce findings on MIF as a factor with cytokine-inducing properties but it has confirmed that MIF is capable of inducing glucocorticoid-counter regulating activity and amplifying LPS-driven cytokine responses. The aim of this review is to analyse the plethora of data surrounding MIF not just as a cytokine, but also as a hormone-like molecule, enzyme with atypical properties and as a thioredoxin-like protein to address fundamental questions about MIF functionality.