is_single() works in plugin, not in theme?

All that I can think of is to verify that you are in fact on a single post page ( echo out an else conditional, make sure that you are actually hitting your block of code ).

if ( is_single() ) {
    echo 'Hello World, Is Single';
} else {
    echo 'Not Single';
}

Where exactly are you placing the code (Header, Body, Footer, which template file)? Are you using any frameworks like Carrington ?