In-program content targeting is described. A default data stream containing default content associated with multiple segments of a particular program is generated and transmitted. An alternate data stream containing alternate content for one or more of the multiple segments is also generated and transmitted. A client device receiving the default content via the default data stream detects the availability of alternate content via the data stream. Based on profile data associated with the client device (or a user of the client device) and profile data associated with the alternate content, the client device may access the alternate data stream for one or more segments of the particular program.