Stress-first approaches to myocardial perfusion imaging provide diagnostically and prognostically accurate perfusion data equivalent to a full rest-stress study, save time in the imaging laboratory, and reduce the radiation exposure to patients and laboratory staff. Converting a nuclear cardiology laboratory from a conventional rest-stress strategy to a stress-first approach involves challenges such as the need for attenuation correction, triage of patients to an appropriate protocol, real-time review of stress images, and consideration of differential reimbursement.