Hotkeys can be used from the Settings window or the Game window. But the application doesn't allow hotkeys that could interfere with user input. So, if you're working on the Game tab, for example, which has a bunch of inputs, hotkeys don't work. It would be rather inconvenient, for example, if you were trying to change the tournament description and every time you pressed the "b" key the application opened the Add-on Players dialog.
You can change this, however. On the Preferences tab, select the Behavior category. Then check the box next to "Allow hotkeys on all Settings tabs that do not have inputs". It's a good 25 or so checkboxes down. This will allow Hotkeys on most tabs.
One other thing: certain hotkeys that won't interfere with inputs: keys F1 through F12 and ESC, can be used from either the Settings or Game window, regardless of this setting, and regardless if there are inputs on the tab or not. If you want the most flexibility, assign your most important hotkeys to these keys.