Efficiently serving large files in a Ruby on Rails application can be achieved using the X-Sendfile or X-Accel-Redirect headers, which allow the web server (like Nginx) to handle file delivery after the application has performed authentication and authorization. This method improves performance, reduces memory usage, and enhances security by offloading the file transfer workload from the application server to the web server. It's particularly beneficial for large, static files but not necessary for small files or dynamically generated content.