Interventions that comprise interdisciplinary collaboration including behavioral elements are effective in addressing lifestyle disease risk factors. However, it is not known how best to conduct this collaboration for sustainable change. The aim of this study was to systematically examine the evidence for the effects of interdisciplinary interventions on lifestyle disease risk factors including weight, lipid levels, glycemic control, and blood pressure. To do so, a systematic review of the literature was conducted using the databases Scopus, Medline, and Web of Science (all years to September 2014). Eighteen articles describing 16 studies of interdisciplinary interventions were identified. Consistent results were found for effects on weight loss but not for effects on blood lipids, blood glucose, and blood pressure. Effective interventions involved collaborations between dieticians, exercise physiologists, and psychologists and incorporated intensive initial participant engagement. Few studies investigated the long-term effect of interventions, but where this was done, the maintenance of favorable changes required ongoing participant support. Current evidence suggests that interdisciplinary interventions are effective in promoting weight loss and that ongoing support of participants is key to maintaining results beyond initial study duration. Future studies should examine long-term effects in pragmatic trials that address translation to practice.