The Internet and related digital technologies have spawned the burgeoning growth of an information revolution in health care. Emerging evidence provides support for the beneficial effects of online interactive eHealth programs, although many challenges remain with respect to research approaches to methodology, implementation, and evaluation. This paper addresses and highlights some of the unique challenges and opportunities that researchers in eHealth face with a particular emphasis on methodologic issues. A brief historical perspective provides context for the subsequent appraisal of the current state of eHealth research. Next, emerging evidence pointing to the growing interest and investment in eHealth research is presented.