In the post-9/11 era, an increasing number of extremist threats are homegrown. Radical organizations such as the Islamic State are actively targeting Muslim immigrants and nationals of Western countries as recruits. Yet, little research has addressed the factors that drive immigrants to aggress against their country of settlement. We integrate the terrorism and immigrant acculturation literatures to suggest that cultural identification processes play a key role in the radicalization of Muslim immigrant and minority populations. Specifically, we propose that "marginalized" immigrants who do not identify with either their heritage culture or the culture of the larger society (Berry, 1970, 1997) have experienced significance loss (Kruglanski, Chen, Dechesne, Fishman, & Orehek, 2009) and are at the greatest risk for radicalization due to threats to significance. Moreover, we argue that this can be exacerbated by exclusion from others in the larger society. In Study 1, we show in a sample of 198 Muslims in the United States that marginalized individuals experience significance loss, which is exacerbated by exclusion from the larger society, and in turn increases support for radical groups, ideologies and behavior. In Study 2, we find partial replication of this model outside the American context in a sample of 204 Muslims in Germany. In Study 3, we move to the lab and demonstrate in a sample of 145 first- and second-generation immigrants in the United States that marginalization, and to some extent exclusion, are risk factors for significance loss outside of the Muslim population, and that significance loss contributes to support for radicalism. Implications for psychological science and social policy are discussed.