How to comment out multiple lines at once in Notepad++?

Select desired lines and then press CTRL+Q. This will toggle comments on and off.

Also, I've just recently become a fan of ALT + Left Mouse Click to select multiple lines and just manually comment those lines with //.

I've found the ALT + Left Mouse Click trick to work well with Visual Studio, JetBrain products, Notepad++ but not Eclipse.

Also CTRL+K works well in Notepad++ to comment. If you had existing comments in a long block you are commenting, CTRL+Q will uncomment your actual comments, where CTRL+K just add another level of // in front. CTRL+SHIFT+K removes a single line comment from the selection.

In notepad++ I believe that the shortcut is CTRL+Q for commenting the code.

You can go to Settings > Shortcut Mapper to change this to match your preference.

The default for a block comment is CTRL+SHIFT+Q. So you can highlight the block of code then use this shortcut.