Background: This study examined how risk perceptions and social norms around e-cigarettes are associated with susceptibility (i.e., openness to using the product in the next 12 months) of e-cigarettes and smoking among adolescents. Methods: We analyzed data from a 2016 representative survey of 8,718 middle school students in Mexico. The study sample was restricted to students who had tried neither e-cigarettes nor cigarettes, (N = 4471). Students reported on the risks of e-cigarettes compared with those of cigarettes, and product-specific norms were measured by assessing current use by family members, at least one close friend, and, for e-cigarettes, by perceived societal acceptability of use (i.e., acceptability among people in general). Adjusted prevalence ratios (APR) were estimated using generalized estimating equation models that regressed e-cigarette societal acceptability on study variables. Adjusted generalized estimating equation models also regressed susceptibility for each product on study variables. Results: Susceptibility to both e-cigarettes and smoking was higher among students who reported that their family and friends used only cigarettes or both products when compared with students whose family and friends did not use either of these products. Friend use of e-cigarettes was associated with e-cigarette susceptibility (APR = 1.33) but not smoking susceptibility. Students who perceived that e-cigarettes were less risky than smoking were more susceptible to e-cigarette use (APR = 1.45). The association between e-cigarette susceptibility and friend or family use was not mediated by societal acceptability. Conclusions: E-cigarette use among family and peers appears associated with susceptibility to use e-cigarettes in a way that is similar to the patterns found for cigarettes. However, the influences appear somewhat specific to the type of product that network members use.