The time is NOW for Lifestyle Medicine. In this review based on a presentation at the American College of Lifestyle Medicine (ACLM) 2021 annual conference, ACLM Current President Cate Collings, MD, Immediate Past-President Dexter Shurney, MD, and President Elect Beth Frates, MD, share insights on the current state of lifestyle medicine (LM). Interest in LM has greatly advanced in the face of disruptions from the COVID-19 pandemic, expanded educational opportunities in the field, and a rapidly changing healthcare landscape. With growing access to virtual care, advancing technologies, growing emphasis on home-based chronic care, continuing corporate healthcare mergers and acquisitions, and widening adoption of personalized, patient-empowered treatments, the time is ripe for LM interventions to move to the mainstream. As health investments and costs skyrocket, and new players enter the scene, traditional models of payments, reimbursements, and incentives are slowly being upended. Companies and healthcare systems are finally recognizing the scientific evidence and powerful but undervalued potential of LM to accelerate healthy outcomes while controlling costs. Taken together, the lessons from the COVID-19 pandemic, the growth in LM educational opportunities, and the evolving "business of medicine landscape" signal that the time for lifestyle medicine is NOW.