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Background: Complexity has been linked to health interventions in two ways: first as a property of the intervention, and secondly as a property of the system into which the intervention is implemented. The former recognizes that interventions may consist of multiple components that act both independently and interdependently, making it difficult to identify the components or combinations of components (and their contexts) that are important mechanisms of change. The latter recognizes that interventions are implemented in complex adaptive systems comprised of intelligent agents who modify their behaviour (including any actions required to implement the intervention) in an effort to improve outcomes relative to their own perspective and objectives. Although an intervention may be intended to take a particular form, its implementation and impact within the system may deviate from its original intentions as a result of adaptation. Complexity highlights the challenge in developing interventions as effective health solutions. The UK Medical Research Council provides guidelines on the development and evaluation of complex interventions. While mathematical modelling is included in the guidelines, there is potential for mathematical modeling to play a greater role.Discussion: The dynamic non-linear nature of complex adaptive systems makes mathematical modelling crucial. However, the tendency is for models of interventions to limit focus on the ecology of the system - the 'real-time' operation of the system and impacts of the intervention. These models are deficient by not modelling the way the system reacts to the intervention via agent adaptation. Complex intervention modelling needs to capture the consequences of adaptation through the inclusion of an evolutionary dynamic to describe the long-term emergent outcomes that result as agents respond to the ecological changes introduced by intervention in an effort to produce better outcomes for themselves. Mathematical approaches such as those found in economics in evolutionary game theory and mechanism design can inform the design and evaluation of health interventions. As an illustration, the introduction of a central screening clinic is modeled as an example of a health services delivery intervention. Complexity necessitates a greater role for mathematical models, especially those that capture the dynamics of human actions and interactions. [ABSTRACT FROM AUTHOR]