TIMTOWTDI, personally I like to be explicit and use non-capturing groups for this kind of thing, like (?: ... )? and/or (?: ... | ... ) (although the former gets a little less readable in the example below). The following regex requires there to be a space before the comment, and I've also used the /x modifier to make it a bit more readable.

while (<DATA>) {
    my ($host,$comment)
        = m{^ \s* (\w+) (?: \s+ \#+ (.*) | \s* ) $}x
        #OR:
        # m{^ \s* (\w+) (?: \s+ (?: \#+ (.*) )? )? $}x
        or die "failed to parse '$_'";
    $hosts{$host} = $comment//'';
}
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Update: Yet another option: m{^ \s* (\w+) \s+ (?: \#+ (.*) )? $}x - this works because even if there's nothing following the \w+, the \s+ will match the newline, and $ matches either at the end of the string or at the newline at the end of the string.