An application host (such as a web application server) may execute a set of applications on behalf of a set of users. Such applications may not be fully trusted, and a two-way isolation of the distributed resources of an application (e.g., the executing application, the application user interface on the user's computer, and server- and client-side stored resources) from other applications may be desirable. This isolation may be promoted utilizing the cross-domain restriction policies of each user's computer by allocating a distinct subdomain of the application host for each application. The routing of network requests to a large number of distinct subdomains may be economized by mapping all distinct subdomains to the address of the domain of the application host. Moreover, the application user interfaces may be embedded in an isolation construct (e.g., an IFRAME HTML element) to promote two-way isolation among application user interfaces and client-side application resources.