The inexorable rising tide of drug resistant pathogens poses multiple challenges. Typically, patients are identified with an acute infection, empiric therapy is initiated, and samples are taken to identify which drugs are effective against a patient's pathogen. Such resistant profile testing can take several days after which the empiric therapy may seem to be suboptimal based on how it performed in the laboratory. This milieu allows naturally for the development of sequentially randomized strategy trials. Patients are initially randomized to an initial empiric therapy and then may be randomized to a second therapy based on the resistance tests. Such a design allows for multiple randomized assessments. Both strategy questions and drug efficacy questions can be addressed. Such studies can be complicated to design and analyze because design parameters may be poorly known and the same patients can contribute to different strategies. This talk develops optimal design and analysis approach for such trials.