Background: Confronted with well-defended, novel hosts, should an enemy invest in avoidance of these hosts (behavioral adaptation), neutralization of the defensive innovation ( physiological adaptation) or both? Although simultaneous investment in both adaptations may first appear to be redundant, several empirical studies have suggested a reinforcement of physiological resistance to host defenses with additional avoidance behaviors. To explain this paradox, we develop a mathematical model describing the joint evolution of behavioral and physiological adaptations on the part of natural enemies to their host defenses. Our specific goals are (i) to derive the conditions that may favor the simultaneous investment in avoidance and physiological resistance and (ii) to study the factors that govern the relative investment in each adaptation mode. Results: Our results show that ( i) a simultaneous investment may be optimal if the fitness costs of the adaptive traits are accelerating and the probability of encountering defended hosts is low. When ( i) holds, we find that ( ii) the more that defended hosts are rare and/or spatially aggregated, the more behavioral adaptation is favored. Conclusion: Despite their interference, physiological resistance to host defensive innovations and avoidance of these same defenses are two strategies in which it may be optimal for an enemy to invest in simultaneously. The relative allocation to each strategy greatly depends on host spatial structure. We discuss the implications of our findings for the management of invasive plant species and the management of pest resistance to new crop protectants or varieties