Costs of defense are central to our understanding of interactions between organisms and their environment, and defensive phenotypes of plants have long been considered to be constrained by trade-offs that reflect the allocation of limiting resources. Recent advances in uncovering signal transduction networks have revealed that defense trade-offs are often the result of regulatory "decisions" by the plant, enabling it to fine-tune its phenotype in response to diverse environmental challenges. We place these results in the context of classic studies in ecology and evolutionary biology, and propose a unifying framework for growth-defense trade-offs as a means to study the plant's allocation of limiting resources. Pervasive physiological costs constrain the upper limit to growth and defense traits, but the diversity of selective pressures on plants often favors negative correlations at intermediate trait levels. Despite the ubiquity of underlying costs of defense, the current challenge is using physiological and molecular approaches to predict the conditions where they manifest as detectable trade-offs.