Monocytes are innate immune cells with diverse functions in host defense against infection and tumors, as well as tissue homeostasis, repair and regeneration. They perform surveillance roles throughout the body and can be rapidly recruited to infected or injured tissues. Recent studies have revealed that monocytes are more heterogeneous than previously appreciated and we have shown that this is in part a reflection of their origins. I will present evidence that functionally distinct monocyte subsets arise via independent pathways in the bone marrow, and discuss how infection, inflammation, cancer and aging may impact monocyte production and functional programming.