Cell migration is essential throughout the life of multicellular organisms, and largely depends on the spatial and temporal regulation of cytoskeletal dynamics, cell adhesion and signal transduction. Interestingly, Estrogen-related receptor alpha (ERRα) has been identified as a major regulator of cell migration in both physiological and pathological conditions. ERRα is an orphan member of the nuclear hormone receptor superfamily of transcription factors and displays many biological functions. ERRα is a global regulator of energy metabolism, and it is also highly involved in bone homeostasis, development, differentiation, immunity and cancer progression. Importantly, in some instances, the regulation of these biological processes relies on the ability to orchestrate cell movements. Therefore, this review describes how ERRα-mediated cell migration contributes not only to tissue homeostasis but also to tumorigenesis and metastasis, and highlights the molecular and cellular mechanisms by which ERRα finely controls the cell migratory potential.