The evolutionary theory of behavior dynamics (ETBD) is a genetic algorithm that applies the Darwinian principles of evolutionary biology to model how behavior changes dynamically via selection by contingencies of reinforcement. The ETBD is a complexity theory where low-level rules of selection, reproduction, and mutation operate iteratively to animate “artificial organisms” that generate emergent outcomes. Numerous studies have demonstrated the ETBD can accurately model behavior of live animals in the laboratory, and it has been applied recently to model automatically maintained self-injury. The purpose of the current series of studies was to further extend the application of the ETBD to model additional functional classes of challenging behavior and clinical procedures. Outcomes obtained with artificial organisms generally corresponded well with outcomes observed with clinical cases sourced from consecutive controlled case series studies. Conceptual and methodological considerations on the application of the ETBD to model challenging behavior are discussed.