For interventions to control infectious diseases, many factors may invalidate standard assumptions underlying the design of clinical trials. These include the existence of indirect (spillover, herd) effects on those in the trial and in the general population, heterogeneity of host susceptibility or of intervention effects, and interplay between the intervention and the natural course of participants' experience of infection and acquisition of immunity. I will describe some of these conditions that make trial design challenging, and then give 3-4 examples of the use of models/simulations (of varying mathematical/computational structure) to assist in the design and evaluation of infectious disease intervention trials.