In this article we argue that the classical—linear and bottom-up directed—models of causation in biology, and the ‘‘proximate/ultimate’’ dichotomy, are inappropriate to capture the complexity inherent to biological processes. We introduce a new notion of ‘‘multilevel causation’’ where old dichotomies such as proximate/ultimate and bottom-up/ top-down are reinterpreted within a multilevel, web-like, approach. In briefly reviewing some recent work on complexity, EvoDevo, carcinogenesis, autocatalysis, comparative genomics, animal regeneration, phenotypic plasticity, and niche construction, we will argue that such reinterpretation is a (...) necessary step for the advancement of the ‘‘Extended Synthesis.’’. (shrink)