The ability of reductionism to advance our understanding of complex biological phenomena is limited. The ecological developmental biology (eco-devo) movement rejects the notion that development is merely the unfolding of a genetic program. Fetal exposure to environmental endocrine disruptors may contribute to the increased incidence of male genital tract malformations, decreased sperm quality, several neoplasms, and altered body weight. Here we discuss problems hindering the study of endocrine disruption (reductionist stance, technically driven research biases, and study of single end points, chemicals and exposure periods). We propose the study of both upward and downward causation and a Systems Biology approach to develop quantitative mathematical models for use in computer simulations that would generate testable predictions. This integrative approach will allow the simultaneous consideration of organismal (systemic) effects and effects on various organ systems. It will promote the identification of similar and unique effects of different endocrine disruptors, and their inter-relationships.