Purpose: Social scientific approach has become an important approach in e-Health studies over the past decade. However, there has been little systematical examination of what aspects of e-Health social scientists have studied and how relevant and informative knowledge has been produced and diffused by this line of inquiry. This study performed a systematic review of the body of e-Health literature in mainstream social science journals over the past decade by testing the applicability of a 5A categorization (i.e., access, availability, appropriateness, acceptability, and applicability), proposed by the U.S. Department of Health and Human Services, as a framework for understanding social scientific research in e-Health. Methods: This study used a quantitative, bottom-up approach to review the e-Health literature in social sciences published from 2000 to 2009. A total of 3005 e-Health studies identified from two social sciences databases (i.e., Social Sciences Citation Index and Arts & Humanities Citation Index) were analyzed with text topic modeling and structural analysis of co-word network, co-citation network, and scientific food web. Results: There have been dramatic increases in the scale of e-Health studies in social sciences over the past decade in terms of the numbers of publications, journal outlets and participating disciplines. The results empirically confirm the presence of the 5A clusters in e-Health research, with the cluster of applicability as the dominant research area and the cluster of availability as the major knowledge producer for other clusters. The network analysis also reveals that the five distinctive clusters share much more in common in research concerns than what e-Health scholars appear to recognize. Conclusions: It is time to explicate and, more importantly, tap into the shared concerns cutting across the seemingly divided scholarly communities. In particular, more synergy exercises are needed to promote adherence of the field.